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1.
Sci Rep ; 12(1): 208, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34996910

RESUMEN

There is limited research into Invasive fungal disease (IFD) in children with no underlying disease. We undertook a retrospective study of children with IFD who did not suffer from another underlying disease, from June 2010 to March 2018 in Changsha, China. Nine children were identified. Eosinophil counts were elevated in six cases. The level of procalcitonin (PCT) was elevated in six cases. Fungal culture was positive in all patients, including eight cases of Cryptococcus neoformans and one case of Candida parapsilosis. 8.33 days following antifungal treatment, the body temperature of the eight patients affected by cryptococcal disease had returned to normal. Our study indicates that the primary pathogen in IFD was Cryptococcus neoformans in children who had no other underlying disease. Eosinophils can be considered to be indicators of cryptococcal infection. IFD in children with no other underlying disease has a satisfactory prognosis.


Asunto(s)
Candida parapsilosis/aislamiento & purificación , Candidiasis/microbiología , Criptococosis/microbiología , Cryptococcus neoformans/aislamiento & purificación , Infecciones Fúngicas Invasoras/microbiología , Adolescente , Antifúngicos/uso terapéutico , Biomarcadores/sangre , Candida parapsilosis/efectos de los fármacos , Candidiasis/sangre , Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Niño , Preescolar , China , Criptococosis/sangre , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Cryptococcus neoformans/efectos de los fármacos , Eosinófilos/microbiología , Femenino , Humanos , Infecciones Fúngicas Invasoras/sangre , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Valor Predictivo de las Pruebas , Polipéptido alfa Relacionado con Calcitonina/sangre , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
2.
Sci Rep ; 11(1): 6364, 2021 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-33737534

RESUMEN

To understand the inflammatory microenvironment and microbiome factors for prognosis of chronic rhinosinusitis with polyps (CRSwNP), we explored the difference in characteristics of the microbiome of the nasal sinuses and inflammatory cytokines between recurrent and non-recurrent groups. We collected nasal secretions and polyp tissue from 77 CRSwNP patients. Then, we extracted microbial DNA from cotton swabs, performed high-throughput sequencing based on 16S rRNA to detect bacterial community composition, and analyzed cytokines such as IL-5, IL-8, IL-17a, IL-17e, IL-18, IL-27 and INF-gamma from polyp tissue using Luminex. The eosinophil and neutrophil cells in the peripheral blood and polyp tissue were counted. Postoperative follow-up of patients with CRSwNP for 1 year was conducted to record the recurrence of nasal polyps and analyze the correlation between the recurrence of nasal polyps and the characteristics of inflammatory cytokines, inflammatory cell count and nasal microbial diversity. After 1 year of follow-up, there were 12 recurrent patients, including 5 males and 7 females. Postoperative recurrence of nasal polyps was not significantly correlated with age, sex, asthma, allergic rhinitis or other allergic diseases in CRSwNP patients. In terms of the total nasal symptom score, the recurrent group was significantly higher than the non-recurrent group. In nasal polyp tissues, eosinophils (40.83/HP) and neutrophils (30.83/HP) in patients with CRSwNP in the recurrent group were significantly higher than those in the non-recurrent group (13.72/HP), and neutrophils (18.5/HP) were also significantly higher in the recurrent group than the non-recurrent group. The expression levels of IFN-, IL-17A, IL-17E and IL-18 were significantly higher in the recurrent group than in the non-recurrent group, and the positive rates were not different. In Southwest China, Enterobacteria and anaerobic bacteria may be correlated with the inflammatory pattern expression of nasal polyps. The neutrophil-mediated inflammatory response plays an important role in patients with CRSwNP in Southwest China and is correlated with nasal polyp recurrence. Recurrence of nasal polyps after endoscopic sinus surgery may be potentially associated with a reduced abundance of protective microorganisms and an increased number of pathogenic microorganisms.


Asunto(s)
Enterobacteriaceae/genética , Inflamación/genética , Microbiota/genética , Pólipos Nasales/microbiología , Adulto , Bacterias/citología , Bacterias/genética , China/epidemiología , Enterobacteriaceae/patogenicidad , Eosinófilos/microbiología , Eosinófilos/patología , Femenino , Humanos , Inflamación/epidemiología , Inflamación/microbiología , Inflamación/patología , Masculino , Persona de Mediana Edad , Mucosa Nasal/microbiología , Mucosa Nasal/patología , Pólipos Nasales/epidemiología , Pólipos Nasales/genética , Pólipos Nasales/patología , Senos Paranasales/microbiología , Senos Paranasales/patología , Pronóstico , ARN Ribosómico 16S/genética , Rinitis/epidemiología , Rinitis/genética , Rinitis/microbiología , Sinusitis/epidemiología , Sinusitis/genética , Sinusitis/microbiología
3.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33431676

RESUMEN

Pathogen interactions arising during coinfection can exacerbate disease severity, for example when the immune response mounted against one pathogen negatively affects defense of another. It is also possible that host immune responses to a pathogen, shaped by historical evolutionary interactions between host and pathogen, may modify host immune defenses in ways that have repercussions for other pathogens. In this case, negative interactions between two pathogens could emerge even in the absence of concurrent infection. Parasitic worms and tuberculosis (TB) are involved in one of the most geographically extensive of pathogen interactions, and during coinfection worms can exacerbate TB disease outcomes. Here, we show that in a wild mammal natural resistance to worms affects bovine tuberculosis (BTB) severity independently of active worm infection. We found that worm-resistant individuals were more likely to die of BTB than were nonresistant individuals, and their disease progressed more quickly. Anthelmintic treatment moderated, but did not eliminate, the resistance effect, and the effects of resistance and treatment were opposite and additive, with untreated, resistant individuals experiencing the highest mortality. Furthermore, resistance and anthelmintic treatment had nonoverlapping effects on BTB pathology. The effects of resistance manifested in the lungs (the primary site of BTB infection), while the effects of treatment manifested almost entirely in the lymph nodes (the site of disseminated disease), suggesting that resistance and active worm infection affect BTB progression via distinct mechanisms. Our findings reveal that interactions between pathogens can occur as a consequence of processes arising on very different timescales.


Asunto(s)
Búfalos/inmunología , Resistencia a la Enfermedad , Hemoncosis/microbiología , Pulmón/inmunología , Ganglios Linfáticos/inmunología , Tricostrongiliasis/microbiología , Tuberculosis Bovina/microbiología , Animales , Antinematodos/farmacología , Búfalos/microbiología , Búfalos/parasitología , Bovinos , Coinfección , Progresión de la Enfermedad , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Eosinófilos/microbiología , Eosinófilos/parasitología , Heces/parasitología , Femenino , Fenbendazol/farmacología , Hemoncosis/tratamiento farmacológico , Hemoncosis/mortalidad , Hemoncosis/parasitología , Haemonchus/efectos de los fármacos , Haemonchus/genética , Haemonchus/patogenicidad , Inmunoglobulina A/sangre , Pulmón/efectos de los fármacos , Pulmón/microbiología , Pulmón/parasitología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/parasitología , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Mastocitos/microbiología , Mastocitos/parasitología , Mycobacterium bovis/crecimiento & desarrollo , Mycobacterium bovis/patogenicidad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tricostrongiliasis/tratamiento farmacológico , Tricostrongiliasis/mortalidad , Tricostrongiliasis/parasitología , Trichostrongylus/efectos de los fármacos , Trichostrongylus/genética , Trichostrongylus/patogenicidad , Tuberculosis Bovina/tratamiento farmacológico , Tuberculosis Bovina/mortalidad , Tuberculosis Bovina/parasitología
4.
Life Sci ; 264: 118685, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33137369

RESUMEN

BACKGROUND: Differentiation of bone marrow eosinophils (BM-EO) and its trafficking to peripheral blood and respiratory mucosa are a hallmark of inflammatory diseases. Staphylococcal enterotoxin B (SEB) has been shown to aggravate airways eosinophilic inflammation. This study aimed to investigate the effects of mouse airways SEB exposure on BM-EO population, as well as its adhesive properties and release of cytokines/chemokines that orchestrate BM-EO trafficking to lungs. METHODS: Male BALB/c mice were intranasally exposed to SEB (1 µg), and at 4, 16, 24 and 48 h thereafter, bone marrow (BM), circulating blood and bronchoalveolar lavage (BAL) fluid were collected. Levels of cytokines/chemokines and expressions of VLA-4 and CCR3 in BM were evaluated. Adhesion of BM to ICAM-1 and VCAM-1 were also evaluated. RESULTS: SEB exposure promoted a marked eosinophil influx to BAL at 16 and 24 h after exposure, which was accompanied by significant increases in counts of immature (16 h) and mature (4 to 48 h) forms of eosinophil in BM, along with blood eosinophilia (16 h). In BM, higher levels of eotaxin, IL-5, IL-4, IL-3 and IL-7 were detected at 16 to 48 h. SEB also significantly increased CCR3 expression and calcium levels in BM-EO, and enhanced the cell adhesion to ICAM-1 (24 h) and ICAM-1 (48 h). CONCLUSION: Airways SEB exposure increases the number of eosinophils in BM by mechanisms involving a network of cytokine and chemokine release, facilitating the BM-EO adhesion to ICAM-1 and VCAM-1 to gain access to the peripheral blood and lung tissues.


Asunto(s)
Administración Intranasal/métodos , Médula Ósea/metabolismo , Enterotoxinas/metabolismo , Eosinófilos/metabolismo , Pulmón/metabolismo , Absorción Nasal/fisiología , Animales , Médula Ósea/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Enterotoxinas/administración & dosificación , Enterotoxinas/sangre , Eosinófilos/microbiología , Pulmón/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Staphylococcus aureus/metabolismo
5.
Ned Tijdschr Geneeskd ; 1642020 05 28.
Artículo en Holandés | MEDLINE | ID: mdl-32749816

RESUMEN

Macrolides are antibiotics with anti-inflammatory properties that may be beneficial in the treatment of asthma. In a systematic review, Hiles et al. analysed the effect of azithromycin in the prevention of asthma exacerbations in patients with severe asthma. In their study they conclude that prolonged treatment with azithromycin (at least 3 months) reduces the number of asthma exacerbations; however, the conclusions of this review should be interpreted carefully as the included studies vary in study design, dosing schedule and severity of the asthma. Additionally, maintenance treatment with macrolides may have safety risks, side-effects and lead to antibiotic resistance. Prolonged macrolide therapy should, therefore, be reserved for patients with non-eosinophilic asthma who have no alternative treatment options.


Asunto(s)
Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Azitromicina/uso terapéutico , Macrólidos/uso terapéutico , Asma/sangre , Asma/microbiología , Progresión de la Enfermedad , Farmacorresistencia Bacteriana/efectos de los fármacos , Eosinófilos/efectos de los fármacos , Eosinófilos/microbiología , Humanos , Revisiones Sistemáticas como Asunto
6.
J Immunol ; 205(4): 1157-1166, 2020 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-32690653

RESUMEN

The cyclooxygenase (COX) metabolic pathway regulates immune responses and inflammation. The effect of the COX pathway on innate pulmonary inflammation induced by protease-containing fungal allergens, such as Alternaria alternata, is not fully defined. In this study, we tested the hypothesis that COX inhibition augments Alternaria-induced pulmonary group 2 innate lymphoid cell (ILC2) responses and IL-33 release. Mice were treated with the COX inhibitors indomethacin, flurbiprofen, or vehicle and challenged intranasally with Alternaria extract for four consecutive days to induce innate lung inflammation. We found that indomethacin and flurbiprofen significantly increased the numbers of ILC2 and IL-5 and IL-13 expression by ILC2 in the lung. Indomethacin also increased ILC2 proliferation, the percentages of eosinophils, and mucus production in the lung. Both indomethacin and flurbiprofen augmented the release of IL-33 in bronchoalveolar lavage fluid after Alternaria challenge, suggesting that more IL-33 was available for ILC2 activation and that a COX product(s) inhibited IL-33 release. This is supported by the in vitro finding that the COX product PGE2 and the PGI2 analogs cicaprost decreased Alternaria extract-induced IL-33 release by human bronchial epithelial cells. Although contrasting effects of PGD2, PGE2, and PGI2 on ILC2 responses have been previously reported, the overall effect of the COX pathway on ILC2 function is inhibitory in Alternaria-induced innate airway inflammation.


Asunto(s)
Alternaria/inmunología , Inhibidores de la Ciclooxigenasa/farmacología , Inmunidad Innata/efectos de los fármacos , Interleucina-33/inmunología , Linfocitos/efectos de los fármacos , Alérgenos/inmunología , Alternariosis/inmunología , Alternariosis/metabolismo , Alternariosis/microbiología , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Proliferación Celular/efectos de los fármacos , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Eosinófilos/microbiología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/microbiología , Femenino , Flurbiprofeno/inmunología , Humanos , Inmunidad Innata/inmunología , Indometacina/farmacología , Interleucina-13/inmunología , Interleucina-5/inmunología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/microbiología , Linfocitos/inmunología , Linfocitos/microbiología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Neumonía/metabolismo , Neumonía/microbiología
7.
Respir Res ; 18(1): 88, 2017 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-28482840

RESUMEN

BACKGROUND: Sputum and blood eosinophil counts predict corticosteroid effects in COPD patients. Bacterial infection causes increased airway neutrophilic inflammation. The relationship of eosinophil counts with airway bacterial load in COPD patients is uncertain. We tested the hypothesis that bacterial load and eosinophil counts are inversely related. METHODS: COPD patients were seen at stable state and exacerbation onset. Sputum was processed for quantitative polymerase chain reaction detection of the potentially pathogenic microorganisms (PPM) H. influenzae, M. catarrhalis and S. pneumoniae. PPM positive was defined as total load ≥1 × 104copies/ml. Sputum and whole blood were analysed for differential cell counts. RESULTS: At baseline, bacterial counts were not related to blood eosinophils, but sputum eosinophil % was significantly lower in patients with PPM positive compared to PPM negative samples (medians: 0.5% vs. 1.25% respectively, p = 0.01). Patients with PPM positive samples during an exacerbation had significantly lower blood eosinophil counts at exacerbation compared to baseline (medians: 0.17 × 109/L vs. 0.23 × 109/L respectively, p = 0.008), while no blood eosinophil change was observed with PPM negative samples. CONCLUSIONS: These findings indicate an inverse relationship between bacterial infection and eosinophil counts. Bacterial infection may influence corticosteroid responsiveness by altering the profile of neutrophilic and eosinophilic inflammation.


Asunto(s)
Eosinófilos/patología , Recuento de Leucocitos , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/patología , Esputo/citología , Esputo/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Carga Bacteriana , Sangre/microbiología , Eosinófilos/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
J Microbiol Methods ; 137: 19-24, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28359737

RESUMEN

Eosinophils are resident leukocytes of gut mucosa. Here we present a combined flow cytometric-antibiotic protection assay to identify mouse eosinophils capable of bacterial uptake, specifically, Gram-positive Lactobacillus reuteri, in studies performed ex vivo. The assay may be adapted for use in vivo.


Asunto(s)
Eosinófilos/microbiología , Citometría de Flujo/métodos , Limosilactobacillus reuteri/metabolismo , Probióticos/farmacocinética , Aminoglicósidos/química , Animales , Escherichia coli/efectos de los fármacos , Granulocitos/microbiología , Mucosa Intestinal/citología , Mucosa Intestinal/microbiología , Kanamicina/farmacología , Limosilactobacillus reuteri/aislamiento & purificación , Ratones , Ratones Endogámicos C57BL
9.
Mucosal Immunol ; 10(1): 194-204, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27049063

RESUMEN

Eosinophils contribute to type II immune responses in helminth infections and allergic diseases; however, their influence on intracellular pathogens is less clear. We previously reported that CCR2-/- mice exposed to the intracellular fungal pathogen Histoplasma capsulatum exhibit dampened immunity caused by an early exaggerated interleukin (IL)-4 response. We sought to identify the cellular source promulgating IL-4 in infected mutant animals. Eosinophils were the principal instigators of non-protective IL-4 and depleting this granulocyte population improved fungal clearance in CCR2-/- animals. The deleterious impact of eosinophilia on mycosis was also recapitulated in transgenic animals overexpressing eosinophils. Mechanistic examination of IL-4 induction revealed that phagocytosis of H. capsulatum via the pattern recognition receptor complement receptor (CR) 3 triggered the heightened IL-4 response in murine eosinophils. This phenomenon was conserved in human eosinophils; exposure of cells to the fungal pathogen elicited a robust IL-4 response. Thus, our findings elucidate a detrimental attribute of eosinophil biology in fungal infections that could potentially trigger a collapse in host defenses by instigating type II immunity.


Asunto(s)
Eosinófilos/inmunología , Histoplasma/inmunología , Histoplasmosis/inmunología , Interleucina-4/metabolismo , Receptores CCR2/metabolismo , Animales , Antígenos Fúngicos/inmunología , Células Cultivadas , Eosinófilos/microbiología , Humanos , Evasión Inmune , Inmunidad Innata , Antígeno de Macrófago-1/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fagocitosis , Receptores CCR2/genética
10.
Laryngoscope ; 127(1): 59-63, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27577717

RESUMEN

BACKGROUND: Chronic rhinosinusitis consists of several disease processes. Eosinophilic mucin is found in the subtypes of allergic fungal sinusitis (AFS) and eosinophilic mucin chronic rhinosinusitis (EMCRS). These entities frequently require surgical intervention and have high recurrence rates. OBJECTIVE: We aimed to determine factors in patients with AFS and EMCRS that may be associated with a higher rate of revision surgeries. Our hypothesis is that patients who have polyps, high Lund-Mackay score (LMS), and fungus may have higher revision rates. STUDY DESIGN: Retrospective cohort study. METHODS: This is a retrospective analysis of 117 patients identified over a 5-year period (2005-2009) with the diagnosis of AFS or EMCRS. Contingency tables were created to obtain the odds ratios estimates, and 95% confidence intervals were used to access the association between the outcome (having revision surgery or not) and other clinical binary predictors. RESULTS: Twenty-six of 117 (22%) of the study patients underwent revision surgery. Within the 2-year follow-up period, an additional five of 26 (19%) required another revision surgery. Average LMS was slightly higher in those who underwent revision surgery (16 vs. 13) on a scale of 0 to 24, with an overall mean score of 18 and standard deviation of 6.82 for the whole sample (117). Other factors evaluated were the presence of fungus, polyps, eosinophilic mucin, and the eosinophilic count and medical therapy received. CONCLUSION: The presence of eosinophilic mucin was significantly associated a higher rate of revision surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:59-63, 2017.


Asunto(s)
Micosis/inmunología , Micosis/microbiología , Micosis/cirugía , Reoperación/estadística & datos numéricos , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/microbiología , Rinitis/inmunología , Rinitis/microbiología , Rinitis/cirugía , Sinusitis/inmunología , Sinusitis/microbiología , Sinusitis/cirugía , Enfermedad Crónica , Eosinófilos/inmunología , Eosinófilos/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucinas/inmunología , Pólipos Nasales/inmunología , Pólipos Nasales/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
12.
Mil Med ; 181(6): e613-5, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27244075

RESUMEN

Acute eosinophilic pneumonia is a rare entity characterized by rapidly progressive infiltration of eosinophils into the lungs and is often associated with drug exposure or infection. We report a case of a previously healthy 19-year-old woman who presented with acute progressive dyspnea. Chest radiograph revealed diffuse bilateral infiltrates. Based on the results of bronchoalveolar lavage fluid and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspect that the disease was related to smoking because she had started smoking 3 weeks before the onset of symptoms. Given the high prevalence of smoking and initiation of smoking in the military population, it is important for physicians taking care of this population to be aware of this disorder.


Asunto(s)
Fumar Cigarrillos/efectos adversos , Eosinofilia Pulmonar/complicaciones , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/fisiopatología , Enfermedad Aguda/terapia , Disnea/etiología , Eosinófilos/metabolismo , Eosinófilos/microbiología , Femenino , Humanos , Recuento de Leucocitos/métodos , Personal Militar , Radiografía Torácica/métodos , Esteroides/farmacología , Esteroides/uso terapéutico , Adulto Joven
13.
BMC Immunol ; 17(1): 12, 2016 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-27245920

RESUMEN

BACKGROUND: Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. RESULTS: Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). CONCLUSIONS: We demonstrate for the first time that there are regional differences in the requirement of eosinophils for maintaining IgA+ cells between the large and small intestine, which are more pronounced during inflammation. This is an important step towards further delineation of the enigmatic functions of gut-resident eosinophils.


Asunto(s)
Eosinófilos/inmunología , Inflamación/inmunología , Intestino Grueso/inmunología , Intestino Delgado/inmunología , Células Plasmáticas/inmunología , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunología , Tricuriasis/inmunología , Trichuris/inmunología , Animales , Células Cultivadas , Microambiente Celular , Eosinófilos/microbiología , Eosinófilos/parasitología , Factor de Transcripción GATA1/genética , Inmunoglobulina A/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Células Plasmáticas/microbiología , Células Plasmáticas/parasitología
14.
Infect Immun ; 84(6): 1879-86, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27068093

RESUMEN

Cryptococcus neoformans is an opportunistic fungal pathogen that is inhaled into the lungs and can lead to life-threatening meningoencephalitis in immunocompromised patients. Currently, the molecular mechanisms that regulate the mammalian immune response to respiratory cryptococcal challenge remain poorly defined. DAP12, a signaling adapter for multiple pattern recognition receptors in myeloid and natural killer (NK) cells, has been shown to play both activating and inhibitory roles during lung infections by different bacteria and fungi. In this study, we demonstrate that DAP12 plays an important inhibitory role in the immune response to C. neoformans Infectious outcomes in DAP12(-/-) mice, including survival and lung fungal burden, are significantly improved compared to those in C57BL/6 wild-type (WT) mice. We find that eosinophils and macrophages are decreased while NK cells are increased in the lungs of infected DAP12(-/-) mice. In contrast to WT NK cells, DAP12(-/-) NK cells are able to repress C. neoformans growth in vitro Additionally, DAP12(-/-) macrophages are more highly activated than WT macrophages, with increased production of tumor necrosis factor (TNF) and CCL5/RANTES and more efficient uptake and killing of C. neoformans These findings suggest that DAP12 acts as a brake on the pulmonary immune response to C. neoformans by promoting pulmonary eosinophilia and by inhibiting the activation and antifungal activities of effector cells, including NK cells and macrophages.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/inmunología , Criptococosis/inmunología , Cryptococcus neoformans/patogenicidad , Regulación Fúngica de la Expresión Génica , Interacciones Huésped-Patógeno , Enfermedades Pulmonares Fúngicas/inmunología , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Quimiocina CCL5/genética , Quimiocina CCL5/inmunología , Criptococosis/genética , Criptococosis/microbiología , Criptococosis/patología , Cryptococcus neoformans/crecimiento & desarrollo , Cryptococcus neoformans/inmunología , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Eosinófilos/microbiología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/microbiología , Pulmón/inmunología , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/genética , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/patología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/microbiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Cultivo Primario de Células , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
15.
Infect Immun ; 83(12): 4594-603, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26371121

RESUMEN

Pneumocystis is a respiratory fungal pathogen that causes pneumonia (Pneumocystis pneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4(+) T cell-dependent clearance of Pneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages for Pneumocystis clearance has not been determined. Therefore, RAG2(-/-) mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected with Pneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2(-/-) mice developed severe disease but effectively cleared Pneumocystis and resolved IRIS. Neither RAG/IFN-γR(-/-) nor RAG/IL-4Rα(-/-) mice displayed impaired Pneumocystis clearance. However, RAG/IFN-γR(-/-) mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα(-/-) mice. RAG/IFN-γR(-/-) mice had elevated numbers of lung CD4(+) T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8(+) T suppressor cells. Impaired lung CD8(+) T cell responses in RAG/IFN-γR(-/-) mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impair Pneumocystis clearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8(+) T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Síndrome Inflamatorio de Reconstitución Inmune/inmunología , Macrófagos Alveolares/inmunología , Pneumocystis/inmunología , Neumonía por Pneumocystis/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Linfocitos T CD8-positivos/microbiología , Linfocitos T CD8-positivos/patología , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Eosinófilos/inmunología , Eosinófilos/microbiología , Eosinófilos/patología , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno , Síndrome Inflamatorio de Reconstitución Inmune/genética , Síndrome Inflamatorio de Reconstitución Inmune/microbiología , Síndrome Inflamatorio de Reconstitución Inmune/patología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/microbiología , Células Asesinas Naturales/patología , Pulmón/inmunología , Pulmón/microbiología , Pulmón/patología , Activación de Macrófagos , Macrófagos Alveolares/microbiología , Macrófagos Alveolares/patología , Ratones , Ratones Noqueados , Ratones SCID , Neutrófilos/inmunología , Neutrófilos/microbiología , Neutrófilos/patología , Pneumocystis/patogenicidad , Neumonía por Pneumocystis/genética , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/patología , Receptores de Superficie Celular/deficiencia , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Receptores de Interferón/deficiencia , Receptores de Interferón/genética , Receptores de Interferón/inmunología , Transducción de Señal , Linfocitos T Colaboradores-Inductores/microbiología , Linfocitos T Colaboradores-Inductores/patología , Balance Th1 - Th2 , Receptor de Interferón gamma
16.
J Immunol ; 195(1): 185-93, 2015 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-25994969

RESUMEN

Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive drug regimens targeting T cell activation are also susceptible. Given the crucial role of CD4(+) T cells in host defense against Pneumocystis, we used RNA sequencing of whole lung early in infection in wild-type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild-type mice, a strong eosinophil signature was observed at day 14 post Pneumocystis challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice were more susceptible to Pneumocystis infection when compared with BALB/c controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden, compared with mice treated with control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development in the treatment of Pneumocystis pneumonia in the immunosuppressed population.


Asunto(s)
Eosinófilos/inmunología , Interleucina-5/inmunología , Pulmón/inmunología , Pneumocystis/inmunología , Neumonía por Pneumocystis/inmunología , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/microbiología , Linfocitos T CD4-Positivos/patología , Eosinófilos/microbiología , Eosinófilos/patología , Femenino , Factor de Transcripción GATA1/deficiencia , Factor de Transcripción GATA1/genética , Factor de Transcripción GATA1/inmunología , Expresión Génica , Terapia Genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/inmunología , Interacciones Huésped-Patógeno , Interleucina-5/genética , Recuento de Leucocitos , Pulmón/microbiología , Pulmón/patología , Activación de Linfocitos , Depleción Linfocítica , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Plásmidos/administración & dosificación , Plásmidos/inmunología , Neumonía por Pneumocystis/genética , Neumonía por Pneumocystis/patología , Neumonía por Pneumocystis/terapia , Factores de Tiempo
17.
J Med Assoc Thai ; 97 Suppl 6: S248-53, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25391201

RESUMEN

Basidiobolus ranarum is an uncommon subcutaneous zygomycosis mostly found in immunocompetent children in tropical countries. Presence of slow growing non-tender, non-inflammatory, subcutaneous swelling that does not spread beyond the subcutaneous tissue are classic clinical features. The authors report two cases of subcutaneous zygomycosis which tissue cultures were positive for Basidiobolus ranarum. The first case was a 10-months-old boy presented with prolonged high fever and a rapidly expanding ulcerated plaque unresponsive to systemic antibiotic. The second case was a 2-years-old girl presented with slow expanding mass at the buttock. Histopathology of both cases showed lobular panniculitis with eosinophilic infiltration and fungal culture revealed Basidiobolus ranarum. Oral itraconazole was given with good clinical response in both cases.


Asunto(s)
Inflamación/tratamiento farmacológico , Itraconazol/uso terapéutico , Cigomicosis/diagnóstico , Administración Oral , Biopsia , Preescolar , Entomophthorales , Eosinófilos/microbiología , Femenino , Fiebre , Humanos , Lactante , Masculino , Tejido Subcutáneo/patología , Cigomicosis/tratamiento farmacológico
18.
Infect Immun ; 82(9): 3723-39, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24958709

RESUMEN

The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.


Asunto(s)
Quimiocina CCL8/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Infecciones por Klebsiella/inmunología , Klebsiella pneumoniae/inmunología , Pulmón/inmunología , Neutrófilos/inmunología , Animales , Eosinófilos/inmunología , Eosinófilos/microbiología , Femenino , Hipersensibilidad/microbiología , Inflamación/microbiología , Interleucinas/inmunología , Infecciones por Klebsiella/microbiología , Pulmón/microbiología , Ratones , Ratones Endogámicos BALB C , Neutrófilos/microbiología , Ovalbúmina/inmunología , Neumonía Bacteriana/inmunología , Neumonía Bacteriana/microbiología
19.
Int Forum Allergy Rhinol ; 4(1): 29-33, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24106210

RESUMEN

BACKGROUND: The influence of the microbial community on inflammatory subtype in chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a product of local flora rather than an intrinsic mucosal process. The associations between culturable bacteria and the histopathology and clinical features of CRS patients are described. METHODS: A cross-sectional study involving patients with CRS undergoing surgery was undertaken. Middle meatal swabs were performed at surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded histopathological profile was performed. Disease specific quality of life and nasal symptom scores were recorded. The presence of culturable organisms and particular pathogens were compared with histopathology and clinical outcomes. RESULTS: A total of 95 patients were assessed (48.4% female, mean age 45.6 ± 14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had neutrophilic infiltrate, with the presence of neither Gram-positive organisms, Gram-negative organisms, nor species correlating to pathology subtype. A culturable pathogen was a predictor of subepithelial fibrosis (χ(2) = 6.36, p = 0.04) and Gram-negative bacteria had the strongest association (χ(2) = 18.82, p < 0.01). There were no other significant associations with other clinical outcomes. CONCLUSION: The culturable bacterial community has little impact on histopathology in CRS. While more sensitive tests may detect bacteria in the sinuses, the impact of the simple "culturable" bacteria on the underlying pathologic process is limited. Changes, such as subepithelial fibrosis, suggest colonization may lead to undesirable local mucosal damage and remodeling.


Asunto(s)
Eosinófilos/microbiología , Cavidad Nasal/microbiología , Rinitis/microbiología , Sinusitis/microbiología , Adulto , Enfermedad Crónica , Estudios Transversales , Eosinófilos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal/patología , Rinitis/patología , Sinusitis/patología , Encuestas y Cuestionarios
20.
Mediators Inflamm ; 2013: 152943, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24082429

RESUMEN

Cell counts of leukocytes subpopulations are demonstrating to have an important value in predicting outcome in severe infections. We evaluated here the render of leukogram counts to predict outcome in patients with ventilator-associated pneumonia (VAP) caused by Staphylococcus aureus. Data from patients admitted to the ICU of Hospital Clínico Universitario de Valladolid from 2006 to 2011 with diagnosis of VAP caused by S. aureus were retrospectively collected for the study (n = 44). Leukocyte counts were collected at ICU admission and also at VAP diagnosis. Our results showed that nonsurvivors had significant lower eosinophil counts at VAP diagnosis. Multivariate Cox regression analysis performed by the Wald test for forward selection showed that eosinophil increments from ICU admission to VAP diagnosis and total eosinophil counts at VAP diagnosis were protective factors against mortality in the first 28 days following diagnosis: (HR [CI 95%], P): (0.996 [0.993-0.999], 0.010); (0.370 [0.180-0.750], 0.006). Patients with eosinophil counts <30 cells/mm(3) at diagnosis died earlier. Eosinophil counts identified survivors: (AUROC [CI 95%], P): (0.701 [0.519-0.882], 0.042). Eosinophil behaves as a protective cell in patients with VAP caused by S. aureus.


Asunto(s)
Eosinófilos/fisiología , Neumonía Estafilocócica/sangre , Neumonía Asociada al Ventilador/sangre , Neumonía Asociada al Ventilador/mortalidad , Anciano , Área Bajo la Curva , Cuidados Críticos , Farmacorresistencia Bacteriana , Eosinófilos/microbiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Neumonía Estafilocócica/mortalidad , Neumonía Asociada al Ventilador/microbiología , Modelos de Riesgos Proporcionales , Análisis de Regresión , Staphylococcus aureus , Resultado del Tratamiento
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