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1.
Epidemiol Infect ; 152: e83, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38705586

RESUMEN

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.


Asunto(s)
Quirópteros , Histoplasma , Histoplasmosis , Animales , Quirópteros/microbiología , Brasil/epidemiología , Histoplasma/genética , Histoplasma/aislamiento & purificación , Histoplasmosis/epidemiología , Histoplasmosis/veterinaria , Histoplasmosis/microbiología , Reacción en Cadena de la Polimerasa/veterinaria
2.
Microb Pathog ; 132: 166-177, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31054870

RESUMEN

The macrophage innate immune response is outlined through recognition of the components of Mycobacterium tuberculosis. DNA of M. tuberculosis (MtbDNA) is recognized by macrophages, but the implications of this recognition are poorly characterized. Stimulation of murine macrophages with MtbDNA induces autophagy, a process that promotes elimination of intracellular pathogens. However, it remains unknown whether this or other phenomena also occur in human cells. In this work, we studied the innate response profiles of human macrophages after stimulation with DNA from virulent M. tuberculosis H37Rv. Human monocyte-derived macrophages were polarized into M1 and M2 phenotypes and stimulated with MtbDNA. The plasma membrane markers of the phenotype, production of TNF-α, and induction of autophagy were evaluated. Our results indicate that MtbDNA induced phenotypical changes, the significant production of TNF-α, and autophagy confirmed by the augmented expression of immunity related GTPase M (IRGM) and autophagy related ATG16L1 genes in M1 macrophages, whereas M2 macrophages exhibited limited responses. In addition, MtbDNA activation was TLR-9-dependent. Although TLR-9 expression was similar between M1 and M2 macrophages, only M1 macrophages were fully responsive to MtbDNA. In conclusion, MtbDNA recognition enhanced the antimicrobial mechanisms of M1 macrophages.


Asunto(s)
Autofagia , ADN Bacteriano/aislamiento & purificación , Macrófagos/metabolismo , Mycobacterium tuberculosis/genética , Factor de Necrosis Tumoral alfa/metabolismo , ADN Bacteriano/genética , Humanos , Inmunidad Innata , Monocitos , Mycobacterium tuberculosis/metabolismo , Fenotipo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo
3.
Respir Res ; 17(1): 66, 2016 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27250970

RESUMEN

Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C-terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways.


Asunto(s)
Enfermedades Pulmonares Fúngicas/metabolismo , Pulmón/metabolismo , Neumonía/metabolismo , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Animales , Citocinas/inmunología , Citocinas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata , Mediadores de Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Pulmón/inmunología , Pulmón/microbiología , Enfermedades Pulmonares Fúngicas/inmunología , Enfermedades Pulmonares Fúngicas/microbiología , Neumonía/inmunología , Neumonía/microbiología , Proteína A Asociada a Surfactante Pulmonar/inmunología , Proteína D Asociada a Surfactante Pulmonar/inmunología
4.
BMC Microbiol ; 14: 23, 2014 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-24495513

RESUMEN

BACKGROUND: Histoplasma capsulatum and Pneumocystis organisms cause host infections primarily affecting the lung tissue. H. capsulatum is endemic in the United States of America and Latin American countries. In special environments, H. capsulatum is commonly associated with bat and bird droppings. Pneumocystis-host specificity has been primarily studied in laboratory animals, and its ability to be harboured by wild animals remains as an important issue for understanding the spread of this pathogen in nature. Bats infected with H. capsulatum or Pneumocystis spp. have been found, with this mammal serving as a probable reservoir and disperser; however, the co-infection of bats with both of these microorganisms has never been explored. To evaluate the impact of H. capsulatum and Pneumocystis spp. infections in this flying mammal, 21 bat lungs from Argentina (AR), 13 from French Guyana (FG), and 88 from Mexico (MX) were screened using nested-PCR of the fragments, employing the Hcp100 locus for H. capsulatum and the mtLSUrRNA and mtSSUrRNA loci for Pneumocystis organisms. RESULTS: Of the 122 bats studied, 98 revealed H. capsulatum infections in which 55 of these bats exhibited this infection alone. In addition, 51 bats revealed Pneumocystis spp. infection of which eight bats exhibited a Pneumocystis infection alone. A total of 43 bats (eight from AR, one from FG, and 34 from MX) were found co-infected with both fungi, representing a co-infection rate of 35.2% (95% CI = 26.8-43.6%). CONCLUSION: The data highlights the H. capsulatum and Pneumocystis spp.co-infection in bat population's suggesting interplay with this wild host.


Asunto(s)
Quirópteros , Coinfección/veterinaria , Histoplasma/aislamiento & purificación , Histoplasmosis/veterinaria , Infecciones por Pneumocystis/veterinaria , Pneumocystis/aislamiento & purificación , Animales , Argentina , Guyana , México , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Ribosómico/genética , Análisis de Secuencia de ADN
5.
Tuberculosis (Edinb) ; 143: 102418, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37813014

RESUMEN

Pulmonary tuberculosis (TB) inflammation is an underestimated disease complication which anti-inflammatory drugs may alleviate. This study explored the potential use of the COX-2 inhibitors acetylsalicylic acid (ASA) and celecoxib in 12 TB patients and 12 healthy controls using a whole-blood ex vivo model where TNFα, PGE2, and LTB4 plasma levels were quantitated by ELISA; we also measured COX-2, 5-LOX, 12-LOX, and 15-LOX gene expression. We observed a significant TNFα production in response to stimulation with LPS or M. tuberculosis (Mtb). Celecoxib, but not ASA, reduced TNFα and PGE2 production, while increasing LTB4 in patients after infection with Mtb. Gene expression of COX-2 and 5-LOX was higher in controls, while 12-LOX was significantly higher in patients. 15-LOX expression was similar in both groups. We concluded that COX-2 inhibitors downregulate inflammation after Mtb infection, and our methodology offers a straightforward time-efficient approach for evaluating different drugs in this context. Further research is warranted to elucidate the underlying mechanisms and assess the potential clinical benefit.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Celecoxib/farmacología , Celecoxib/uso terapéutico , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Dinoprostona , Inmunidad , Inflamación/metabolismo , Leucotrieno B4/metabolismo , Mycobacterium tuberculosis/metabolismo , Tuberculosis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa
6.
Front Immunol ; 14: 1241121, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37753080

RESUMEN

Introduction: Pulmonary dysfunction is an underestimated complication in tuberculosis (TB) infection, affecting quality of life (QoL). Although respiratory function tests objectively reflect lung disturbances in a specific moment, predictors of illness severity at the time of diagnosis are still lacking. Methods: We measured serum pro-inflammatory cytokines (TNF-α and IL-8), eicosanoids (PGE2, LTB4, RvD1, Mar1, and LXA4), a marker of tissue damage (cell-free nucleosomes), and indicators of redox status (malonaldehyde, 8-isoprostane, total oxidants, and antioxidants), as well as a score of radiological abnormalities (SRA) and a QoL questionnaire, in 25 patients with pulmonary TB at the time of diagnosis (t0) and two months after the initiation of treatment (t2). Results: We found higher antioxidant levels in the patients with the worst QoL at t0, and all the indicators of the prooxidant state were significantly reduced at t2, while the total antioxidant levels increased. LTB4, a pro-inflammatory eicosanoid, was diminished at t2, while all the pro-resolutory lipids decreased substantially. Significant correlations between the SRA and the QoL scores were observed, the latter showing a substantial reduction at t2, ranking it as a reliable tool for monitoring disease evolution during TB treatment. Discussion: These results suggest that evaluating a combination of these markers might be a valuable predictor of QoL improvement and a treatment response indicator; in particular, the oxidation metabolites and eicosanoid ratios could also be proposed as a future target for adjuvant therapies to reduce inflammation-associated lung injury in TB disease.


Asunto(s)
Tuberculosis Latente , Tuberculosis Pulmonar , Humanos , Calidad de Vida , Antioxidantes , Leucotrieno B4 , Tuberculosis Pulmonar/tratamiento farmacológico , Cognición
7.
Biomedicines ; 11(4)2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37189696

RESUMEN

Severe inflammatory responses are associated with the misbalance of innate and adaptive immunity. TLRs, NLRs, and cytokine receptors play an important role in pathogen sensing and intracellular control, which remains unclear in COVID-19. This study aimed to evaluate IL-8 production in blood cells from COVID-19 patients in a two-week follow-up evaluation. Blood samples were taken at admission (t1) and after 14 days of hospitalization (t2). The functionality of TLR2, TLR4, TLR7/8, TLR9, NOD1, and NOD2 innate receptors and IL-12 and IFN-γ cytokine receptors was evaluated by whole blood stimulation with specific synthetic receptor agonists through the quantification of IL-8, TNF-α, or IFN-γ. At admission, ligand-dependent IL-8 secretion was 6.4, 13, and 2.5 times lower for TLR2, TLR4, and endosomal TLR7/8 receptors, respectively, in patients than in healthy controls. Additionally, IL-12 receptor-induced IFN-γ secretion was lower in COVID-19 patients than in healthy subjects. We evaluated the same parameters after 14 days and observed significantly higher responses for TLR2, TLR4, TLR7/8, TLR9, and NOD1, NOD2, and IFN-γ receptors. In conclusion, the low secretion of IL-8 through stimulation with agonists of TLR2, TLR4, TLR7/8, TLR9, and NOD2 at t1 suggests their possible contribution to immunosuppression following hyperinflammation in COVID-19 disease.

8.
Expert Opin Biol Ther ; 23(3): 293-304, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36843568

RESUMEN

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Proteína C-Reactiva/análisis , Inducción de Remisión , Italia , Fármacos Gastrointestinales/uso terapéutico , Resultado del Tratamiento , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico
9.
NPJ Vaccines ; 8(1): 67, 2023 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-37164959

RESUMEN

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

10.
Appl Environ Microbiol ; 78(22): 8122-36, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23001662

RESUMEN

Bats belong to a wide variety of species and occupy diversified habitats, from cities to the countryside. Their different diets (i.e., nectarivore, frugivore, insectivore, hematophage) lead Chiroptera to colonize a range of ecological niches. These flying mammals exert an undisputable impact on both ecosystems and circulation of pathogens that they harbor. Pneumocystis species are recognized as major opportunistic fungal pathogens which cause life-threatening pneumonia in severely immunocompromised or weakened mammals. Pneumocystis consists of a heterogeneous group of highly adapted host-specific fungal parasites that colonize a wide range of mammalian hosts. In the present study, 216 lungs of 19 bat species, sampled from diverse biotopes in the New and Old Worlds, were examined. Each bat species may be harboring a specific Pneumocystis species. We report 32.9% of Pneumocystis carriage in wild bats (41.9% in Microchiroptera). Ecological and behavioral factors (elevation, crowding, migration) seemed to influence the Pneumocystis carriage. This study suggests that Pneumocystis-host association may yield much information on Pneumocystis transmission, phylogeny, and biology in mammals. Moreover, the link between genetic variability of Pneumocystis isolated from populations of the same bat species and their geographic area could be exploited in terms of phylogeography.


Asunto(s)
Portador Sano/veterinaria , Variación Genética , Pulmón/microbiología , Pneumocystis/clasificación , Pneumocystis/genética , Neumonía por Pneumocystis/veterinaria , Animales , Portador Sano/microbiología , Quirópteros , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Mitocondrial/química , ADN Mitocondrial/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Datos de Secuencia Molecular , Filogenia , Pneumocystis/aislamiento & purificación , Neumonía por Pneumocystis/microbiología , Análisis de Secuencia de ADN
11.
Biomolecules ; 12(4)2022 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-35454079

RESUMEN

There is a sex bias in tuberculosis's severity, prevalence, and pathogenesis, and the rates are higher in men. Immunological and physiological factors are fundamental contributors to the development of the disease, and sex-related factors could play an essential role in making women more resistant to severe forms of the disease. In this study, we evaluated sex-dependent differences in inflammatory markers. Serum samples were collected from 34 patients diagnosed with pulmonary TB (19 male and 15 female) and 27 healthy controls (18 male and 9 female). Cytokines IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα, and GM-CSF, and eicosanoids PGE2, LTB4, RvD1, and Mar1 were measured using commercially available immunoassays. The MDA, a product of lipidic peroxidation, was measured by detecting thiobarbituric-acid-reactive substances (TBARS). Differential inflammation patterns between men and women were observed. Men had higher levels of IL6, IL8, and TNFα than women. PGE2 and LTB4 levels were higher in patients than healthy controls, but there were no differences for RvD1 and Mar1. Women had higher RvD1/PGE2 and RvD1/LTB4 ratios among patients. RvD1 plays a vital role in resolving the inflammatory process of TB in women. Men are the major contributors to the typical pro-inflammatory profile observed in the serum of tuberculosis patients.


Asunto(s)
Tuberculosis Pulmonar , Tuberculosis , Dinoprostona , Eicosanoides , Femenino , Humanos , Inflamación/complicaciones , Interleucina-6 , Interleucina-8 , Leucotrieno B4 , Masculino , Tuberculosis/complicaciones , Tuberculosis Pulmonar/complicaciones , Factor de Necrosis Tumoral alfa
12.
World J Clin Cases ; 10(30): 10921-10930, 2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36338227

RESUMEN

BACKGROUND: There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden. AIM: To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy. METHODS: We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit. RESULTS: Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy. CONCLUSION: Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.

13.
medRxiv ; 2022 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-35169806

RESUMEN

There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

14.
Antioxidants (Basel) ; 10(10)2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34679707

RESUMEN

Tuberculosis (TB) is one of the highest infectious burdens worldwide. An excess of inflammation and inadequate antioxidant defense mechanisms are believed to lead to chronic inflammation and lung damage in tuberculosis (TB). However, circulating metabolites do not always replicate lung-associated biomarkers that define the pathobiology of the disease. The objective of this study was to determine the utility of exhaled breath condensate (EBC), a non-invasive and straightforward sample, to evaluate alveolar space-derived metabolites of redox state and inflammation. We assessed the levels of exhaled oxidant/antioxidant parameters (8-isoprostane, MDA, GSH), inflammatory markers, such as nucleosomes, cytokines (IL-2, IL-4, IL-6 and IL-8, IL-10, GM-CSF, TNF-α, and IFN-γ) and lipid mediators (PGE2, LTB4, RvD1, and Mar1), in patients with recently diagnosed pulmonary TB and healthy controls' EBC and serum. The TB patients showed 36% lower GSH levels, and 2-, 1.4-, 1.1-, and 50-fold higher levels of 8-isoprostanes, nucleosomes, IL-6, and LTB4, respectively, in EBC. There was no correlation between EBC and serum, highlighting the importance of measuring local biomarkers. Quantitation of local inflammatory molecules and redox states in EBC would help find biomarkers useful for pharmacological and follow-up studies in pulmonary tuberculosis.

15.
Infect Drug Resist ; 14: 929-946, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727834

RESUMEN

The diagnosis of tuberculosis (TB) in children is difficult because of the low sensitivity and specificity of traditional microbiology techniques in this age group. Whereas in adults the culture of Mycobacterium tuberculosis (M. tuberculosis), the gold standard test, detects 80% of positive cases, it only detects around 30-40% of cases in children. The new methods based on the immune response to M. tuberculosis infection could be affected by many factors. It is necessary to evaluate the medical record, clinical features, presence of drug-resistant M. tuberculosis strains, comorbidities, and BCG vaccination history for the diagnosis in children. There is no ideal biomarker for all TB cases in children. A new strategy based on personalized diagnosis could be used to evaluate specific molecules produced by the host immune response and make therapeutic decisions in each child, thereby changing standard immunological signatures to personalized signatures in TB. In this way, immune diagnosis, prognosis, and the use of potential immunomodulators as adjunct TB treatments will meet personalized treatment.

16.
J Fungi (Basel) ; 7(11)2021 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-34829225

RESUMEN

Histoplasmosis and pneumocystosis co-infections have been reported mainly in immunocompromised humans and in wild animals. The immunological response to each fungal infection has been described primarily using animal models; however, the host response to concomitant infection is unknown. The present work aimed to evaluate the pulmonary immunological response of patients with pneumonia caused either by Histoplasma capsulatum, Pneumocystis jirovecii, or their co-infection. We analyzed the pulmonary collectin and cytokine patterns of 131 bronchoalveolar lavage samples, which included HIV and non-HIV patients infected with H. capsulatum, P. jirovecii, or both fungi, as well as healthy volunteers and HIV patients without the studied fungal infections. Our results showed an increased production of the surfactant protein-A (SP-A) in non-HIV patients with H. capsulatum infection, contrasting with HIV patients (p < 0.05). Significant differences in median values of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, IL-33, IL-13, and CXCL8 were found among all the groups studied, suggesting that these cytokines play a role in the local inflammatory processes of histoplasmosis and pneumocystosis. Interestingly, non-HIV patients with co-infection and pneumocystosis alone showed lower levels of SP-A, IL-1ß, TNF-α, IFN-γ, IL-18, IL-17A, and IL-23 than histoplasmosis patients, suggesting an immunomodulatory ability of P. jirovecii over H. capsulatum response.

17.
J Immunol Res ; 2020: 8235149, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33005692

RESUMEN

Childhood tuberculosis (TB) is a significant public health problem and the ninth leading cause of death worldwide. Progression of Mycobacterium tuberculosis infection to active disease depends on mycobacterial virulence, environmental diversity, and host susceptibility and immune response. In children, malnutrition and immaturity of the immune system contribute to an inadequate immune response. Coinfections, though rarely described in TB, might be associated with host immune deficiencies. Here, we describe the immunological evaluation of eight pediatric patients infected with a member of the M. tuberculosis complex, most of them with concomitant pulmonary infections (bacteria, viruses, or fungi). We assessed the functionality of several innate immunity receptors, IL-12 receptor, and IFN-γ receptor, as well as the antioxidant levels (glutathione), which are essential mechanisms for fighting intracellular pathogens such as M. tuberculosis. This study is aimed at developing a thorough immunological evaluation of patients with TB and a coinfection.


Asunto(s)
Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Adolescente , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Biomarcadores , Niño , Preescolar , Citocinas/metabolismo , Manejo de la Enfermedad , Susceptibilidad a Enfermedades/inmunología , Femenino , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Innata , Lactante , Masculino , Estrés Oxidativo , Medicina de Precisión/métodos , Receptores Toll-Like/metabolismo , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología
18.
Int J Infect Dis ; 86: 65-72, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31207386

RESUMEN

BACKGROUND: Histoplasma capsulatum and Pneumocystis jirovecii are respiratory fungal pathogens that principally cause pulmonary disease. Coinfection with both pathogens is scarcely reported. This study detected this coinfection using specific molecular methods for each fungus in the bronchoalveolar lavage (BAL) of patients from a tertiary care hospital. MATERIALS AND METHODS: BAL samples from 289 hospitalized patients were screened by PCR with specific markers for H. capsulatum (Hcp100) and P. jirovecii (mtLSUrRNA and mtSSUrRNA). The presence of these pathogens was confirmed by the generated sequences for each marker. The clinical and laboratory data for the patients were analyzed using statistical software. RESULTS: The PCR findings separated three groups of patients, where the first was represented by 60 (20.8%) histoplasmosis patients, the second by 45 (15.6%) patients with pneumocystosis, and the last group by 12 (4.2%) patients with coinfection. High similarity among the generated sequences of each species was demonstrated by BLASTn and neighbor-joining algorithms. The estimated prevalence of H. capsulatum and P. jirovecii coinfection was higher in HIV patients.


Asunto(s)
Coinfección/epidemiología , Histoplasmosis/epidemiología , Pneumocystis carinii , Neumonía por Pneumocystis/epidemiología , Adulto , Anciano , Lavado Broncoalveolar , Femenino , Infecciones por VIH/complicaciones , Histoplasma/genética , Histoplasma/aislamiento & purificación , Histoplasmosis/microbiología , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Pneumocystis carinii/genética , Pneumocystis carinii/aislamiento & purificación , Neumonía por Pneumocystis/microbiología , Reacción en Cadena de la Polimerasa , Centros de Atención Terciaria
19.
FEMS Immunol Med Microbiol ; 45(3): 435-41, 2005 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-16061362

RESUMEN

Three isolates of Histoplasma capsulatum were identified from mice lung, liver, and spleen inoculated with soil samples of the X hotel's ornamental potted plants that had been fertilized with organic material known as compost. The presence of H. capsulatum in the original compost was detected using the dot-enzyme-linked immunosorbent assay. Nested-PCR, using a specific protein Hcp100 coding gene sequence, confirmed the fungal identification associated with an unusual histoplasmosis outbreak in Acapulco. Although, diversity between the H. capsulatum isolate from the hotel and some clinical isolates from Guerrero (positive controls) was observed using random amplification of polymorphic DNA based-PCR, sequence analyses of H-anti and ole fragment genes revealed a high homology (92-99%) between them.


Asunto(s)
Brotes de Enfermedades , Histoplasma/aislamiento & purificación , Histoplasmosis/epidemiología , Microbiología del Suelo , Viaje , Animales , Ensayo de Inmunoadsorción Enzimática , Proteínas Fúngicas/genética , Histoplasma/clasificación , Histoplasma/genética , Histoplasma/patogenicidad , Histoplasmosis/microbiología , Histoplasmosis/patología , Humanos , México/epidemiología , Ratones , Ratones Endogámicos BALB C , Especificidad de Órganos , Reacción en Cadena de la Polimerasa , Técnica del ADN Polimorfo Amplificado Aleatorio , Análisis de Secuencia de ADN
20.
Biomed Res Int ; 2015: 982429, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26106622

RESUMEN

Healthcare-associated infections (HAI) are described in diverse settings. The main etiologic agents of HAI are bacteria (85%) and fungi (13%). Some factors increase the risk for HAI, particularly the use of medical devices; patients with severe cuts, wounds, and burns; stays in the intensive care unit, surgery, and hospital reconstruction works. Several fungal HAI are caused by Candida spp., usually from an endogenous source; however, cross-transmission via the hands of healthcare workers or contaminated devices can occur. Although other medically important fungi, such as Blastomyces dermatitidis, Paracoccidioides brasiliensis, and Histoplasma capsulatum, have never been considered nosocomial pathogens, there are some factors that point out the pros and cons for this possibility. Among these fungi, H. capsulatum infection has been linked to different medical devices and surgery implants. The filamentous form of H. capsulatum may be present in hospital settings, as this fungus adapts to different types of climates and has great dispersion ability. Although conventional pathogen identification techniques have never identified H. capsulatum in the hospital environment, molecular biology procedures could be useful in this setting. More research on H. capsulatum as a HAI etiologic agent is needed, since it causes a severe and often fatal disease in immunocompromised patients.


Asunto(s)
Infección Hospitalaria/etiología , Infección Hospitalaria/microbiología , Equipos y Suministros/microbiología , Histoplasma/patogenicidad , Blastomyces/patogenicidad , Candida/patogenicidad , Infección Hospitalaria/epidemiología , Infección Hospitalaria/patología , Humanos , Paracoccidioides/patogenicidad
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