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1.
Rev. int. med. cienc. act. fis. deporte ; 23(92): 313-322, aug.-sept. 2023. graf
Artículo en Inglés | IBECS | ID: ibc-229406

RESUMEN

Objective: This study aims to explore the correlation between interleukin-6 (IL-6) levels and the condition of patients with psittacosis pneumonia, and extend these insights to the context of respiratory health in athletes.Methods: In a retrospective analysis, we included 14 patients diagnosed with psittacosis pneumonia (parrot fever) treated in our hospital from April 2018 to September 2021 as the study group (SG). As a control group (CG), we selected 20 patients with common pneumonia treated during the same period. We compared IL-6 levels between these groups and recorded changes in IL-6 levels in the SG before and after treatment. Additionally, we analyzed the correlation of IL-6 levels with procalcitonin (PCT) and C-reactive protein (CRP) levels.Results:The IL-2 levels in the SG were significantly lower than those in the CG, while IL-6 levels were significantly higher. No significant difference was observed in IL-10 and IL-6 levels between the groups (P>0.05). The average IL-6 level in the SG was 80.78±46.20 ng/L before treatment and 7.86±6.73 ng/L after treatment, showing a significant reduction (P<0.05). There was a significant positive correlation between IL-6 levels and PCT levels in the SG (r=0.2659, P<0.05), but the correlation with CRP levels was not significant (r=0.0033, P=0.8465). The Area Under Curve (AUC) of IL-6 for diagnosing psittacosis pneumonia was 0.7929 (P=0.0041). Conclusion: Patients with psittacosis pneumonia exhibit distinct interleukin level changes, particularly in IL-2 and IL-6, compared to those with ordinary pneumonia. The correlation of IL-6 with PCT levels suggests its potential as a marker in assessing respiratory health conditions, which could be relevant for monitoring respiratory health in athletes, given the heightened susceptibility to respiratory issues in this group (AU)


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , /sangre , Psitacosis/diagnóstico , Psitacosis/inmunología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/inmunología , Estudios Retrospectivos , Biomarcadores/sangre
2.
Front Cell Infect Microbiol ; 13: 1191806, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37424774

RESUMEN

Pseudomonas aeruginosa is a common cause of hospital-acquired infections, including central line-associated bloodstream infections and ventilator-associated pneumonia. Unfortunately, effective control of these infections can be difficult, in part due to the prevalence of multi-drug resistant strains of P. aeruginosa. There remains a need for novel therapeutic interventions against P. aeruginosa, and the use of monoclonal antibodies (mAb) is a promising alternative strategy to current standard of care treatments such as antibiotics. To develop mAbs against P. aeruginosa, we utilized ammonium metavanadate, which induces cell envelope stress responses and upregulates polysaccharide expression. Mice were immunized with P. aeruginosa grown with ammonium metavanadate and we developed two IgG2b mAbs, WVDC-0357 and WVDC-0496, directed against the O-antigen lipopolysaccharide of P. aeruginosa. Functional assays revealed that WVDC-0357 and WVDC-0496 directly reduced the viability of P. aeruginosa and mediated bacterial agglutination. In a lethal sepsis model of infection, prophylactic treatment of mice with WVDC-0357 and WVDC-0496 at doses as low as 15 mg/kg conferred 100% survival against challenge. In both sepsis and acute pneumonia models of infection, treatment with WVDC-0357 and WVDC-0496 significantly reduced bacterial burden and inflammatory cytokine production post-challenge. Furthermore, histopathological examination of the lungs revealed that WVDC-0357 and WVDC-0496 reduced inflammatory cell infiltration. Overall, our results indicate that mAbs directed against lipopolysaccharide are a promising therapy for the treatment and prevention of P. aeruginosa infections.


Asunto(s)
Anticuerpos Antibacterianos , Anticuerpos Monoclonales , Lipopolisacáridos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Animales , Femenino , Ratones , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Adhesión Bacteriana , Carga Bacteriana/inmunología , Convalecencia , Mediadores de Inflamación/inmunología , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/inmunología , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/prevención & control , Pseudomonas aeruginosa/inmunología , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/prevención & control , Sepsis/inmunología , Sepsis/microbiología , Sepsis/prevención & control
3.
Microbiol Spectr ; 10(6): e0311022, 2022 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-36255321

RESUMEN

Nontuberculous mycobacteria (NTM) cause pulmonary disease in individuals without obvious immunodeficiency. This study was initiated to gain insight into the immunological factors that predispose persons to NTM pulmonary disease (NTMPD). Blood was obtained from 15 pairs of NTMPD patients and their healthy household contacts. Peripheral blood mononuclear cells (PBMCs) were stimulated with the Mycobacterium avium complex (MAC). A total of 34 cytokines and chemokines were evaluated in plasma and PBMC culture supernatants using multiplex immunoassays, and gene expression in the PBMCs was determined using real-time PCR. PBMCs from NTMPD patients produced significantly less interleukin-1ß (IL-1ß), IL-18, IL-1α, and IL-10 than PBMCs from their healthy household contacts in response to MAC. Although plasma RANTES levels were high in NTMPD patients, they had no effect on IL-1ß production by macrophages infected with MAC. Toll-like receptor 2 (TLR2) and TWIK2 (a two-pore domain K+ channel) were impaired in response to MAC in PBMCs of NTMPD patients. A TLR2 inhibitor decreased all four cytokines, whereas a two-pore domain K+ channel inhibitor decreased the production of IL-1ß, IL-18, and IL-1α, but not IL-10, by MAC-stimulated PBMCs and monocytes. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. A reduced monocyte ratio might contribute to the attenuated production of IL-1 family cytokines by PBMCs of NTMPD patients in response to MAC stimulations. Collectively, our findings suggest that the attenuated IL-1 response may increase susceptibility to NTM pulmonary infection through multiple factors, including impaired expression of the TLR2 and TWIK2 and reduced monocyte ratio. IMPORTANCE Upon MAC stimulation, the production of IL-1 family cytokines and IL-10 by PBMCs of NTMPD patients was attenuated compared with that of healthy household contacts. Upon MAC stimulation, the expression of TLR2 and TWIK2 (one of the two-pore domain K+ channels) was attenuated in PBMCs of NTMPD patients compared with that of healthy household contacts. The production of IL-1 family cytokines by MAC-stimulated PBMCs and MAC-infected monocytes of healthy donors was reduced by a TLR2 inhibitor and two-pore domain K+ channel inhibitor. The ratio of monocytes was reduced in whole blood of NTMPD patients compared with that of healthy household contacts. Collectively, our data suggest that defects in the expression of TLR2 and TWIK2 in human PBMCs or monocytes and reduced monocyte ratio are involved in the reduced production of IL-1 family cytokines, and it may increase susceptibility to NTM pulmonary infection.


Asunto(s)
Citocinas , Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Neumonía Bacteriana , Humanos , Interleucina-18/inmunología , Leucocitos Mononucleares , Enfermedades Pulmonares/inmunología , Monocitos/inmunología , Complejo Mycobacterium avium , Infecciones por Mycobacterium no Tuberculosas/inmunología , Receptor Toll-Like 2/inmunología , Neumonía Bacteriana/inmunología , Citocinas/inmunología
4.
J Leukoc Biol ; 112(3): 499-512, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35435271

RESUMEN

Clearance of airway intruders by immune cells is required to resolve infectious pneumonia. However, the molecular mechanisms underlying this process remain elusive. Here, we demonstrated that alveolar macrophage (AM)-derived neuropilin 2 (NRP2) plays an essential role in controlling severe pneumonia by enhancing microbial clearance. Mice with conditional deletion of the NRP2 gene in AM had persistent bacteria, uncontrolled neutrophil influx, and decreased survival during Escherichia coli-induced pneumonia. In vitro assays demonstrated that NRP2 could bind to CD11b+ Ly6Glo/+ neutrophils and promote their capacities in phagocytosis and killing of bacteria, which is partially contributed to the increased expression of TLR4 and TNF-a. These findings collectively revealed that AM-derived NRP2 protects the lungs from unwanted injury by promoting the clearance of invading pathogens. This study might provide a promising diagnostic biomarker and therapeutic target for severe pneumonia.


Asunto(s)
Infecciones por Escherichia coli , Macrófagos Alveolares , Neuropilina-2 , Neumonía Bacteriana , Animales , Infecciones por Escherichia coli/inmunología , Pulmón , Lesión Pulmonar , Macrófagos Alveolares/inmunología , Ratones , Ratones Endogámicos C57BL , Neuropilina-2/metabolismo , Neutrófilos , Fagocitosis , Neumonía Bacteriana/inmunología
5.
Viruses ; 14(2)2022 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-35215805

RESUMEN

The increased plasma levels of von Willebrand factor (VWF) in patients with COVID-19 was reported in many studies, and its correlation with disease severity and mortality suggest its important role in the pathogenesis of thrombosis in COVID-19. We performed histological and immunohistochemical studies of the lungs of 29 patients who died from COVID-19. We found a significant increase in the intensity of immunohistochemical reaction for VWF in the pulmonary vascular endothelium when the disease duration was more than 10 days. In the patients who had thrombotic complications, the VWF immunostaining in the pulmonary vascular endothelium was significantly more intense than in nonsurvivors without thrombotic complications. Duration of disease and thrombotic complications were found to be independent predictors of increased VWF immunostaining in the endothelium of pulmonary vessels. We also revealed that bacterial pneumonia was associated with increased VWF staining intensity in pulmonary arterial, arteriolar, and venular endothelium, while lung ventilation was an independent predictor of increased VWF immunostaining in arterial endothelium. The results of the study demonstrated an important role of endothelial VWF in the pathogenesis of thrombus formation in COVID-19.


Asunto(s)
COVID-19/complicaciones , Pulmón/irrigación sanguínea , Trombosis de la Vena/etiología , Trombosis de la Vena/patología , Factor de von Willebrand/análisis , Adulto , Autopsia , COVID-19/sangre , Endotelio Vascular/inmunología , Femenino , Humanos , Inmunohistoquímica/métodos , Pulmón/patología , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/inmunología , Embolia Pulmonar , Índice de Severidad de la Enfermedad , Trombosis de la Vena/clasificación
6.
PLoS One ; 17(1): e0261750, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34986178

RESUMEN

BACKGROUND: In the nation-wide double-blind cluster-randomised Finnish Invasive Pneumococcal disease trial (FinIP, ClinicalTrials.gov NCT00861380, NCT00839254), we assessed the indirect impact of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against five pneumococcal disease syndromes. METHODS: Children 6 weeks to 18 months received PHiD-CV10 in 48 clusters or hepatitis B/A-vaccine as control in 24 clusters according to infant 3+1/2+1 or catch-up schedules in years 2009-2011. Outcome data were collected from national health registers and included laboratory-confirmed and clinically suspected invasive pneumococcal disease (IPD), hospital-diagnosed pneumonia, tympanostomy tube placements (TTP) and outpatient antimicrobial prescriptions. Incidence rates in the unvaccinated population in years 2010-2015 were compared between PHiD-CV10 and control clusters in age groups <5 and ≥5 years (5-7 years for TTP and outpatient antimicrobial prescriptions), and in infants <3 months. PHiD-CV10 was introduced into the Finnish National Vaccination Programme (PCV-NVP) for 3-month-old infants without catch-up in 9/2010. RESULTS: From 2/2009 to 10/2010, 45398 children were enrolled. Vaccination coverage varied from 29 to 61% in PHiD-CV10 clusters. We detected no clear differences in the incidence rates between the unvaccinated cohorts of the treatment arms, except in single years. For example, the rates of vaccine-type IPD, non-laboratory-confirmed IPD and empyema were lower in PHiD-CV10 clusters compared to control clusters in 2012, 2015 and 2011, respectively, in the age-group ≥5 years. CONCLUSIONS: This is the first report from a clinical trial evaluating the indirect impact of a PCV against clinical outcomes in an unvaccinated population. We did not observe consistent indirect effects in the PHiD-CV10 clusters compared to the control clusters. We consider that the sub-optimal trial vaccination coverage did not allow the development of detectable indirect effects and that the supervening PCV-NVP significantly diminished the differences in PHiD-CV10 vaccination coverage between the treatment arms.


Asunto(s)
Proteínas Bacterianas/administración & dosificación , Proteínas Portadoras/administración & dosificación , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae/inmunología , Inmunoglobulina D/administración & dosificación , Lipoproteínas/administración & dosificación , Vacunas Neumococicas/administración & dosificación , Neumonía Bacteriana/prevención & control , Proteínas Bacterianas/efectos adversos , Proteínas Bacterianas/inmunología , Proteínas Portadoras/efectos adversos , Proteínas Portadoras/inmunología , Niño , Preescolar , Método Doble Ciego , Femenino , Infecciones por Haemophilus/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Humanos , Inmunoglobulina D/efectos adversos , Inmunoglobulina D/inmunología , Lactante , Lipoproteínas/efectos adversos , Lipoproteínas/inmunología , Masculino , Vacunas Neumococicas/efectos adversos , Vacunas Neumococicas/inmunología , Neumonía Bacteriana/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología
7.
Nat Med ; 28(1): 201-211, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34782790

RESUMEN

Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated genes and activated IL-1R2+ neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.


Asunto(s)
COVID-19/inmunología , Citocinas/inmunología , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Neutrófilos/inmunología , Neumonía Bacteriana/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Adulto , Anciano , COVID-19/complicaciones , COVID-19/genética , Comunicación Celular , Cromatografía Liquida , Regulación hacia Abajo , Femenino , Redes Reguladoras de Genes , Humanos , Inmunidad Innata/inmunología , Interferones/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/genética , Prostaglandinas/inmunología , Proteómica , RNA-Seq , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/genética , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores Sexuales , Análisis de la Célula Individual , Espectrometría de Masas en Tándem , Tratamiento Farmacológico de COVID-19
8.
JCI Insight ; 7(2)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34908534

RESUMEN

Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome, constituted by respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal, and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, key outstanding questions are whether COVID-19 drives a unique program of neutrophil activation or effector functions that contribute to the severe pathogenesis of this pandemic illness and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single-cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS, compared with those with non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps. Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.


Asunto(s)
COVID-19/inmunología , Trampas Extracelulares/inmunología , Activación Neutrófila , Neutrófilos/inmunología , Síndrome de Dificultad Respiratoria/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/patología , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/patología , Síndrome de Dificultad Respiratoria/patología , Índice de Severidad de la Enfermedad
9.
Viruses ; 13(12)2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34960788

RESUMEN

Influenza A viruses (IAVs) are important respiratory pathogens of horses and humans. Infected individuals develop typical respiratory disorders associated with the death of airway epithelial cells (AECs) in infected areas. Virulence and risk of secondary bacterial infections vary among IAV strains. The IAV non-structural proteins, NS1, PB1-F2, and PA-X are important virulence factors controlling AEC death and host immune responses to viral and bacterial infection. Polymorphism in these proteins impacts their function. Evidence from human and mouse studies indicates that upon IAV infection, the manner of AEC death impacts disease severity. Indeed, while apoptosis is considered anti-inflammatory, necrosis is thought to cause pulmonary damage with the release of damage-associated molecular patterns (DAMPs), such as interleukin-33 (IL-33). IL-33 is a potent inflammatory mediator released by necrotic cells, playing a crucial role in anti-viral and anti-bacterial immunity. Here, we discuss studies in human and murine models which investigate how viral determinants and host immune responses control AEC death and subsequent lung IL-33 release, impacting IAV disease severity. Confirming such data in horses and improving our understanding of early immunologic responses initiated by AEC death during IAV infection will better inform the development of novel therapeutic or vaccine strategies designed to protect life-long lung health in horses and humans, following a One Health approach.


Asunto(s)
Virus de la Influenza A/inmunología , Interleucina-33/inmunología , Infecciones por Orthomyxoviridae/inmunología , Animales , Apoptosis , Asma , Muerte Celular , Células Epiteliales , Caballos , Humanos , Gripe Humana/virología , Pulmón/inmunología , Pulmón/virología , Ratones , Infecciones por Orthomyxoviridae/virología , Neumonía Bacteriana/inmunología , Virulencia , Factores de Virulencia/metabolismo
10.
Front Immunol ; 12: 761317, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34777376

RESUMEN

Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.


Asunto(s)
Citocinas/inmunología , Neumonía Bacteriana/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Femenino , Humanos , Klebsiella pneumoniae , Elastasa de Leucocito/inmunología , Pulmón/citología , Pulmón/inmunología , Macrófagos Alveolares/inmunología , Masculino , Persona de Mediana Edad , Neutrófilos/inmunología , Peroxidasa/inmunología , Adulto Joven
11.
Iran J Allergy Asthma Immunol ; 20(5): 537-549, 2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34664813

RESUMEN

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are considered as a global serious problem in hospitalized patients because of emerging antibiotic resistance. Immunotherapy approaches are promising to prevent such infections. In our previous study, five antigenic epitopes of outer membrane protein A (OmpA), as the most dangerous virulence molecule in A. baumanii, were predicted in silico. In this study, the investigators evaluated some immunological aspects of the peptides. Five peptides were separately injected into C5BL/6 mice; then the cytokine production (interleukin-4 and interferon-gamma) of splenocytes and opsonophagocytic activity of immunized serum were assessed. To identify the protective function of the peptides, animal models of sepsis and pneumonia infections were actively and passively immunized with selected peptides and pooled sera of immunized mice, respectively. Then, survival rates of them were compared with the non-infected controls. Based on the results, activated spleen cells in P127 peptide-immunized mice exhibited an increase level of IFN-γ compared with the other experimental groups, but not about the IL-4 concentration. The results of opsonophagocytic assay revealed an appropriate killing activity of produced antibodies against A. baumannii in a dose-dependent manner. Further, the survival rates of the mice under passive immunization with the immunized sera or active immunization with P127 peptide were significantly more than those in the control group. Moreover, the survival rate of the P127 peptide immunized group was considerably higher than that among the other peptide-immunized group. In conclusion, findings indicated that peptides derived from outer membrane protein-A can be used as a promising tool for designing the epitope-based vaccines against infections caused by A. baumannii.


Asunto(s)
Infecciones por Acinetobacter/prevención & control , Acinetobacter baumannii/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Epítopos/inmunología , Neumonía Bacteriana/prevención & control , Sepsis/prevención & control , Infecciones por Acinetobacter/inmunología , Infecciones por Acinetobacter/mortalidad , Animales , Antígenos Bacterianos/inmunología , Vacunas Bacterianas/administración & dosificación , Citocinas/metabolismo , Modelos Animales de Enfermedad , Interacciones Huésped-Patógeno/inmunología , Inmunización , Ratones , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/mortalidad , Pronóstico , Sepsis/inmunología , Sepsis/mortalidad , Resultado del Tratamiento
12.
Elife ; 102021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34544549

RESUMEN

Vaccination strategies for rapid protection against multidrug-resistant bacterial infection are very important, especially for hospitalized patients who have high risk of exposure to these bacteria. However, few such vaccination strategies exist due to a shortage of knowledge supporting their rapid effect. Here, we demonstrated that a single intranasal immunization of inactivated whole cell of Acinetobacter baumannii elicits rapid protection against broad A. baumannii-infected pneumonia via training of innate immune response in Rag1-/- mice. Immunization-trained alveolar macrophages (AMs) showed enhanced TNF-α production upon restimulation. Adoptive transfer of immunization-trained AMs into naive mice mediated rapid protection against infection. Elevated TLR4 expression on vaccination-trained AMs contributed to rapid protection. Moreover, immunization-induced rapid protection was also seen in Pseudomonas aeruginosa and Klebsiella pneumoniae pneumonia models, but not in Staphylococcus aureus and Streptococcus pneumoniae model. Our data reveal that a single intranasal immunization induces rapid and efficient protection against certain Gram-negative bacterial pneumonia via training AMs response, which highlights the importance and the possibility of harnessing trained immunity of AMs to design rapid-effecting vaccine.


Asunto(s)
Infecciones por Acinetobacter/prevención & control , Acinetobacter baumannii/inmunología , Vacunas Bacterianas/administración & dosificación , Infecciones por Klebsiella/prevención & control , Klebsiella pneumoniae/inmunología , Macrófagos Alveolares/efectos de los fármacos , Neumonía Bacteriana/prevención & control , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa/inmunología , Infecciones por Acinetobacter/inmunología , Infecciones por Acinetobacter/microbiología , Administración Intranasal , Traslado Adoptivo , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Proteínas de Homeodominio/genética , Inmunidad Innata/efectos de los fármacos , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Macrófagos Alveolares/trasplante , Ratones Endogámicos C57BL , Ratones Noqueados , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Factores de Tiempo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Vacunación , Vacunas de Productos Inactivados/administración & dosificación
13.
Food Funct ; 12(19): 9466-9475, 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34473137

RESUMEN

Chlorogenic acid (CGA) possesses a wide variety of bioactive properties, such as antioxidation, anti-inflammation and anti-bacteria. This study was aimed at exploring the effects of CGA of anti-inflammation and anti-bacteria on mouse pneumonia prepared by immunosuppressed mice infected with Klebsiella pneumoniae (K. pneumoniae) in vivo and the cellular inflammasomes through lipopolysaccharide (LPS) and adenosine triphosphate (ATP)-induced RAW 264.7 murine macrophages in vitro. Mice received CGA treatment (30 and 90 mg kg-1) for 8 consecutive days and on the fourth day immunosuppression in mice was induced by cyclophosphamide (40 mg kg-1) for 5 days before inoculation of K. pneumoniae. Immunosuppressed mice infected with K. pneumoniae developed severe pneumonia, with marked interstitial vascular congestion, widened alveolar intervals, infiltration of monocytes, lymphocytes and macrophages as well as the damage of epithelial architecture, with growing mortality and count forming unit (CFU). CGA treatment significantly decreased the ratio of lung/body weight, reduced the severity of pneumonia induced by K. pneumoniae, decreased the lung injury, inflammatory cell infiltration scores and CD68 protein expression, inhibited the expression of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and elevated the expression of IL-10. Meanwhile, we investigated the mechanism of CGA to counter K. pneumoniae-induced pneumonia and found that CGA remarkably repressed the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome. Altogether, our results indicate that the dietary intake of CGA or its rich foods ameliorates K. pneumonia-induced pneumonia by inhibiting the activation of NLRP3 inflammasomes.


Asunto(s)
Ácido Clorogénico/uso terapéutico , Tolerancia Inmunológica , Inflamasomas/metabolismo , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neumonía Bacteriana/tratamiento farmacológico , Animales , Ácido Clorogénico/farmacología , Citocinas/genética , Citocinas/metabolismo , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/metabolismo , Infecciones por Klebsiella/patología , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/metabolismo , Neumonía Bacteriana/patología , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos
14.
PLoS One ; 16(8): e0250133, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34437551

RESUMEN

The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide ß-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C՛1q) onto PNAG were determined by ELISA, and then associated with either clinical pneumonia at Farm A (n = 119) or subclinical pneumonia at Farm B (n = 114). Data were analyzed using multivariable logistic regression. Among RE HIP-transfused foals, the odds of pneumonia were approximately 6-fold higher (P = 0.0005) among foals with VapA antibody activity ≤ the population median. Among PNAG HIP-transfused foals, the odds of pneumonia were approximately 3-fold (P = 0.0347) and 11-fold (P = 0.0034) higher for foals with antibody activities ≤ the population median for PNAG or C՛1q deposition, respectively. Results indicated that levels of activity of antibodies against R. equi antigens are correlates of protection against both subclinical and clinical R. equi pneumonia in field settings. Among PNAG HIP-transfused foals, activity of antibodies with C՛1q deposition (an indicator of functional antibodies) were a stronger predictor of protection than was PNAG antibody activity alone. Collectively, these findings suggest that the amount and activity of antibodies in HIP (i.e., plasma volume and/or antibody activity) is positively associated with protection against R. equi pneumonia in foals.


Asunto(s)
Acetilglucosamina/inmunología , Infecciones por Actinomycetales/veterinaria , Anticuerpos Antibacterianos/uso terapéutico , Proteínas Bacterianas/inmunología , Enfermedades de los Caballos/prevención & control , Inmunización Pasiva/veterinaria , Neumonía Bacteriana/veterinaria , Rhodococcus equi/inmunología , Infecciones por Actinomycetales/inmunología , Infecciones por Actinomycetales/microbiología , Infecciones por Actinomycetales/prevención & control , Animales , Animales Recién Nacidos/inmunología , Animales Recién Nacidos/microbiología , Anticuerpos Antibacterianos/inmunología , Femenino , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/microbiología , Caballos/inmunología , Caballos/microbiología , Inmunización Pasiva/métodos , Masculino , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/prevención & control
15.
PLoS One ; 16(8): e0256166, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34383849

RESUMEN

As electronic cigarette (E-cig) use, also known as "vaping", has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.


Asunto(s)
Calcio/metabolismo , Mezclas Complejas/efectos adversos , Infecciones por Klebsiella/etiología , Klebsiella pneumoniae/patogenicidad , Neumonía Bacteriana/etiología , Vapeo/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Quimiotaxis/inmunología , Sistemas Electrónicos de Liberación de Nicotina , Expresión Génica , Humanos , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Infecciones por Klebsiella/inmunología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/patología , Klebsiella pneumoniae/fisiología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Macrófagos/microbiología , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/patología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
16.
Br J Anaesth ; 127(3): 405-414, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34229832

RESUMEN

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.


Asunto(s)
Infecciones Bacterianas/microbiología , Transfusión de Eritrocitos/efectos adversos , Huésped Inmunocomprometido , Atención Perioperativa/efectos adversos , Procedimientos Quirúrgicos Operativos/efectos adversos , Antibacterianos/uso terapéutico , Bacteriemia/inmunología , Bacteriemia/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/mortalidad , Cuidados Críticos , Transfusión de Eritrocitos/mortalidad , Humanos , Tiempo de Internación , Readmisión del Paciente , Atención Perioperativa/mortalidad , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Procedimientos Quirúrgicos Operativos/mortalidad , Infección de la Herida Quirúrgica/inmunología , Infección de la Herida Quirúrgica/microbiología , Factores de Tiempo , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento
17.
Life Sci ; 281: 119764, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34186045

RESUMEN

AIMS: Although intrauterine growth restriction (IUGR) impairs immune system homeostasis and lung development, its relationship with the susceptibility to pulmonary infections remains unclear. Thus, this study aimed to investigate the impact of IUGR on acute lung inflammatory response induced by bacterial stimulus. MATERIALS AND METHODS: Pregnant female Wistar rats were subjected to 50% caloric-protein food restriction during gestation. To mimic bacterial lung infection, adult male offspring (12 weeks old) were challenged with a single lipopolysaccharide (LPS) intranasal instillation, and 6 h later, we assessed the acute inflammatory response. Normal birth weight (NBW) animals represent the control group. KEY FINDINGS: LPS instillation increased the protein levels in the airways of both the NBW and low birth weight (LBW) groups, indicating vascular leakage. LBW animals exhibited a lower number of neutrophils, reduced production of interleukin-6 and macrophage-inflammatory protein-2 and decreased upregulation of intercellular adhesion molecule-1 gene expression in lung tissues. Further analysis revealed that the LBW group produced lower levels of prostaglandin-E2 and failed to secrete leukotriene-B4 upon LPS stimulation, which correlated with impaired cyclooxygenase-2 and 5-lipoxygenase expression. These results were probably associated with their inability to upregulate the expression of Toll-like receptor-4 and downstream signaling proteins, such as nuclear factor kappa-B, in the lungs. The LBW group also exhibited abnormal airway thickening and high corticosterone levels under basal conditions. SIGNIFICANCE: This study suggests that IUGR-induced foetal programming in LBW offspring threatens HPA axis physiology and corticosterone biodisponibility, and impairs the innate response to bacterial antigens, increasing future susceptibility to pulmonary infection.


Asunto(s)
Corticosterona/biosíntesis , Susceptibilidad a Enfermedades , Retardo del Crecimiento Fetal , Neumonía Bacteriana/inmunología , Efectos Tardíos de la Exposición Prenatal , Animales , Ácido Araquidónico/metabolismo , Femenino , Sistema Hipotálamo-Hipofisario/metabolismo , Lipopolisacáridos/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , FN-kappa B/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Embarazo , Ratas , Ratas Wistar , Receptor Toll-Like 4/metabolismo
18.
Front Immunol ; 12: 629281, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968022

RESUMEN

Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c+ cells led to greatly reduced AM abundance in the lung due to the impaired self-renewal of AMs but not the impeded pre-AM differentiation. Mice with Lkb1-deficient AMs exhibited deteriorated diseases during airway Staphylococcus aureus (S. aureus) infection and allergic inflammation, with excessive accumulation of neutrophils and more severe lung pathology. Drug-mediated AM depletion experiments in wild type mice indicated a cause for AM reduction in aggravated diseases in Lkb1 conditional knockout mice. Transcriptomic sequencing also revealed that Lkb1 inhibited proinflammatory pathways, including IL-17 signaling and neutrophil migration, which might also contribute to the protective function of Lkb1 in AMs. We thus identified Lkb1 as a pivotal regulator that maintains the self-renewal and immune function of AMs.


Asunto(s)
Asma/enzimología , Autorrenovación de las Células , Pulmón/enzimología , Macrófagos Alveolares/enzimología , Neumonía Bacteriana/enzimología , Proteínas Serina-Treonina Quinasas/metabolismo , Infecciones Estafilocócicas/enzimología , Proteínas Quinasas Activadas por AMP , Animales , Asma/genética , Asma/inmunología , Antígenos CD11/genética , Antígenos CD11/metabolismo , Modelos Animales de Enfermedad , Homeostasis , Interleucina-17/genética , Interleucina-17/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Ratones Endogámicos C57BL , Ratones Noqueados , Infiltración Neutrófila , Neumonía Bacteriana/genética , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Transcriptoma
19.
Front Immunol ; 12: 672523, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968082

RESUMEN

Lower respiratory infections are among the leading causes of morbidity and mortality worldwide. These potentially deadly infections are further exacerbated due to the growing incidence of antimicrobial resistance. To combat these infections there is a need to better understand immune mechanisms that promote microbial clearance. This need in the context of lung infections has been further heightened with the emergence of SARS-CoV-2. Group 3 innate lymphoid cells (ILC3s) are a recently discovered tissue resident innate immune cell found at mucosal sites that respond rapidly in the event of an infection. ILC3s have clear roles in regulating mucosal immunity and tissue homeostasis in the intestine, though the immunological functions in lungs remain unclear. It has been demonstrated in both viral and bacterial pneumonia that stimulated ILC3s secrete the cytokines IL-17 and IL-22 to promote both microbial clearance as well as tissue repair. In this review, we will evaluate regulation of ILC3s during inflammation and discuss recent studies that examine ILC3 function in the context of both bacterial and viral pulmonary infections.


Asunto(s)
COVID-19/inmunología , Inmunidad Mucosa/inmunología , Linfocitos/inmunología , Neumonía Bacteriana/inmunología , Mucosa Respiratoria/inmunología , SARS-CoV-2/inmunología , Bacterias/inmunología , COVID-19/mortalidad , COVID-19/patología , Inmunidad Innata/inmunología , Inflamación/inmunología , Interleucina-17/metabolismo , Interleucinas/metabolismo , Pulmón/inmunología , Activación de Linfocitos/inmunología , Mucosa Respiratoria/citología , Interleucina-22
20.
J Surg Res ; 265: 212-222, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33951586

RESUMEN

BACKGROUND: Sepsis induces gut barrier dysfunction characterized by increased gut epithelial apoptosis and increased intestinal permeability. The cytokine IL-22 has been demonstrated to regulate gut barrier function. Type-3 innate lymphoid cells (ILC3) are the predominate source of IL-22 in the GI tract. We hypothesized that sepsis may cause changes to the gut ILC3/IL-22 axis. MATERIALS AND METHODS: Sepsis was induced in WT and IL-22 KO mice by Pseudomonas aeruginosa pneumonia. Changes in gut-associated leukocyte populations were determined by flow-cytometry and ILC-associated transcripts were measured by RT-PCR. The effect of sepsis on gut permeability, pulmonary microbial burden, gut epithelial apoptosis, and survival was compared between WT and IL-22-/- mice. RESULTS: Sepsis resulted in a significant decrease in the number of ILC3 in the gut, with a reciprocal increase in type-1 ILC (ILC1). Consistent with prior reports, sepsis was associated with increased gut permeability; however there was no difference in gut permeability, gut epithelial apoptosis, pulmonary microbial burden, or survival between WT and IL-22-/- mice. CONCLUSIONS: Septic pneumonia causes a decrease in gut-associated ILC3 and an associated reciprocal increase in ILC1. This may reflect inflammation-induced conversion of ILC3 to ILC1. Constitutive systemic IL-22 deficiency does not alter sepsis-induced gut barrier dysfunction.


Asunto(s)
Mucosa Intestinal/inmunología , Linfocitos , Neumonía Bacteriana/inmunología , Infecciones por Pseudomonas/inmunología , Sepsis/inmunología , Animales , Masculino , Ratones Endogámicos C57BL , Neumonía Bacteriana/complicaciones , Infecciones por Pseudomonas/complicaciones
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