Cargando…
In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology
BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in hum...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812093/ https://www.ncbi.nlm.nih.gov/pubmed/24205424 http://dx.doi.org/10.1371/journal.pntd.0002512 |
_version_ | 1782288931392323584 |
---|---|
author | Costa, Tânia A. Bazan, Silvia B. Feriotti, Claudia Araújo, Eliseu F. Bassi, Ênio J. Loures, Flávio V. Calich, Vera L. G. |
author_facet | Costa, Tânia A. Bazan, Silvia B. Feriotti, Claudia Araújo, Eliseu F. Bassi, Ênio J. Loures, Flávio V. Calich, Vera L. G. |
author_sort | Costa, Tânia A. |
collection | PubMed |
description | BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT) and IL-10(−/−) C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb) infection. We verified that Pb-infected peritoneal macrophages from IL-10(−/−) mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10(−/−) and WT mice were i.t. infected with 1×10(6) Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(−/−) mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(−/−) mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+) and CD8(+) T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(−/−) mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a detrimental effect to pulmonary PCM due to its suppressive effect on the innate and adaptive immunity resulting in progressive infection and precocious mortality of infected hosts. |
format | Online Article Text |
id | pubmed-3812093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38120932013-11-07 In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology Costa, Tânia A. Bazan, Silvia B. Feriotti, Claudia Araújo, Eliseu F. Bassi, Ênio J. Loures, Flávio V. Calich, Vera L. G. PLoS Negl Trop Dis Research Article BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT) and IL-10(−/−) C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb) infection. We verified that Pb-infected peritoneal macrophages from IL-10(−/−) mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10(−/−) and WT mice were i.t. infected with 1×10(6) Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(−/−) mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(−/−) mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+) and CD8(+) T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(−/−) mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a detrimental effect to pulmonary PCM due to its suppressive effect on the innate and adaptive immunity resulting in progressive infection and precocious mortality of infected hosts. Public Library of Science 2013-10-24 /pmc/articles/PMC3812093/ /pubmed/24205424 http://dx.doi.org/10.1371/journal.pntd.0002512 Text en © 2013 Costa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Costa, Tânia A. Bazan, Silvia B. Feriotti, Claudia Araújo, Eliseu F. Bassi, Ênio J. Loures, Flávio V. Calich, Vera L. G. In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title | In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title_full | In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title_fullStr | In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title_full_unstemmed | In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title_short | In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology |
title_sort | in pulmonary paracoccidioidomycosis il-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812093/ https://www.ncbi.nlm.nih.gov/pubmed/24205424 http://dx.doi.org/10.1371/journal.pntd.0002512 |
work_keys_str_mv | AT costataniaa inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT bazansilviab inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT feriotticlaudia inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT araujoeliseuf inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT bassienioj inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT louresflaviov inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology AT calichveralg inpulmonaryparacoccidioidomycosisil10deficiencyleadstoincreasedimmunityandregressiveinfectionwithoutenhancingtissuepathology |