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Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis
The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is cons...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120880/ https://www.ncbi.nlm.nih.gov/pubmed/21731741 http://dx.doi.org/10.1371/journal.pone.0021423 |
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author | Cavassani, Karen A. Tristao, Fabrine S. M. Oliveira, Leandro L. Rocha, Fernanda A. Vancim, Jaqueline O. Moreira, Ana Paula Campanelli, Ana Paula Panagio, Luciano A. Milanezi, Cristiane M. Martinez, Roberto Rossi, Marcos A. Silva, Joao S. |
author_facet | Cavassani, Karen A. Tristao, Fabrine S. M. Oliveira, Leandro L. Rocha, Fernanda A. Vancim, Jaqueline O. Moreira, Ana Paula Campanelli, Ana Paula Panagio, Luciano A. Milanezi, Cristiane M. Martinez, Roberto Rossi, Marcos A. Silva, Joao S. |
author_sort | Cavassani, Karen A. |
collection | PubMed |
description | The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is consequence of a Th1-mediated adaptive immune response. In the present study we investigated the mechanisms involved in the immunoregulation triggered after a prior contact with cell-free antigens (CFA) during a murine model of PCM. The results showed that the inoculation of CFA prior to the infection resulted in disorganized granulomatous lesions and increased fungal replication in the lungs, liver and spleen, that paralleled with the higher levels of IL-4 when compared with the control group. The role of IL-4 in facilitating the fungal growth was demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The injection of CFA did not affect the fungal growth in these mice, which, in fact, exhibited a significant diminished amount of fungus in the tissues and smaller granulomas. Considering that in vivo anti-IL-4-application started one week after the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the mediation of the observed unresponsiveness. Further, the characterization of CFA indicated that a proteic fraction is required for triggering the immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties are not. Taken together, our data suggest that the prior contact with soluble Pb antigens leads to severe PCM in an IL-4 dependent manner. |
format | Online Article Text |
id | pubmed-3120880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31208802011-06-30 Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis Cavassani, Karen A. Tristao, Fabrine S. M. Oliveira, Leandro L. Rocha, Fernanda A. Vancim, Jaqueline O. Moreira, Ana Paula Campanelli, Ana Paula Panagio, Luciano A. Milanezi, Cristiane M. Martinez, Roberto Rossi, Marcos A. Silva, Joao S. PLoS One Research Article The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is consequence of a Th1-mediated adaptive immune response. In the present study we investigated the mechanisms involved in the immunoregulation triggered after a prior contact with cell-free antigens (CFA) during a murine model of PCM. The results showed that the inoculation of CFA prior to the infection resulted in disorganized granulomatous lesions and increased fungal replication in the lungs, liver and spleen, that paralleled with the higher levels of IL-4 when compared with the control group. The role of IL-4 in facilitating the fungal growth was demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The injection of CFA did not affect the fungal growth in these mice, which, in fact, exhibited a significant diminished amount of fungus in the tissues and smaller granulomas. Considering that in vivo anti-IL-4-application started one week after the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the mediation of the observed unresponsiveness. Further, the characterization of CFA indicated that a proteic fraction is required for triggering the immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties are not. Taken together, our data suggest that the prior contact with soluble Pb antigens leads to severe PCM in an IL-4 dependent manner. Public Library of Science 2011-06-22 /pmc/articles/PMC3120880/ /pubmed/21731741 http://dx.doi.org/10.1371/journal.pone.0021423 Text en Cavassani 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 Cavassani, Karen A. Tristao, Fabrine S. M. Oliveira, Leandro L. Rocha, Fernanda A. Vancim, Jaqueline O. Moreira, Ana Paula Campanelli, Ana Paula Panagio, Luciano A. Milanezi, Cristiane M. Martinez, Roberto Rossi, Marcos A. Silva, Joao S. Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title | Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title_full | Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title_fullStr | Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title_full_unstemmed | Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title_short | Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis |
title_sort | cell-free antigens from paracoccidioides brasiliensis drive il-4 production and increase the severity of paracoccidioidomycosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120880/ https://www.ncbi.nlm.nih.gov/pubmed/21731741 http://dx.doi.org/10.1371/journal.pone.0021423 |
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