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TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis

Toll-like receptors (TLRs) comprise the best-characterized pattern-recognition receptor (PRR) family able to activate distinct immune responses depending on the receptor/adaptor set assembled. TLRs, such as TLR2, TLR4 and TLR9, and their signaling were shown to be important in Paracoccidioides brasi...

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Autores principales: Jannuzzi, Grasielle Pereira, de Almeida, José Roberto Fogaça, Amarante-Mendes, Gustavo P., Romera, Lavínia Maria Dal'Mas, Kaihami, Gilberto Hideo, Vasconcelos, José Ronnie, Ferreira, Camila Pontes, de Almeida, Sandro Rogério, Ferreira, Karen Spadari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335947/
https://www.ncbi.nlm.nih.gov/pubmed/30687643
http://dx.doi.org/10.3389/fcimb.2018.00426
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author Jannuzzi, Grasielle Pereira
de Almeida, José Roberto Fogaça
Amarante-Mendes, Gustavo P.
Romera, Lavínia Maria Dal'Mas
Kaihami, Gilberto Hideo
Vasconcelos, José Ronnie
Ferreira, Camila Pontes
de Almeida, Sandro Rogério
Ferreira, Karen Spadari
author_facet Jannuzzi, Grasielle Pereira
de Almeida, José Roberto Fogaça
Amarante-Mendes, Gustavo P.
Romera, Lavínia Maria Dal'Mas
Kaihami, Gilberto Hideo
Vasconcelos, José Ronnie
Ferreira, Camila Pontes
de Almeida, Sandro Rogério
Ferreira, Karen Spadari
author_sort Jannuzzi, Grasielle Pereira
collection PubMed
description Toll-like receptors (TLRs) comprise the best-characterized pattern-recognition receptor (PRR) family able to activate distinct immune responses depending on the receptor/adaptor set assembled. TLRs, such as TLR2, TLR4 and TLR9, and their signaling were shown to be important in Paracoccidioides brasiliensis infections. However, the role of the endosomal TLR3 in experimental paracoccidioidomycosys remains obscure. In vitro assays, macrophages of the bone marrow of WT or TLR3(−/−) mice were differentiated for evaluation of their microbicidal activity. In vivo assays, WT or TLR3(−/−) mice were infected intratracheally with Paracoccidioides brasiliensis yeasts for investigation of the lung response type induced. The cytotoxic activity of CD8(+) T cells was assessed by cytotoxicity assay. To confirm the importance of CD8(+) T cells in the control of infection in the absence of tlr3, a depletion assay of these cells was performed. Here, we show for the first time that TLR3 modulate the infection against Paracoccidioides brasiliensis by dampening pro-inflammatory response, NO production, IFN(+)CD8(+)T, and IL-17(+)CD8(+)T cell activation and cytotoxic function, associated with granzyme B and perforin down regulation. As conclusion, we suggest that TLR3 could be used as an escape mechanism of the fungus in an experimental paracoccidioidomycosis.
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spelling pubmed-63359472019-01-25 TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis Jannuzzi, Grasielle Pereira de Almeida, José Roberto Fogaça Amarante-Mendes, Gustavo P. Romera, Lavínia Maria Dal'Mas Kaihami, Gilberto Hideo Vasconcelos, José Ronnie Ferreira, Camila Pontes de Almeida, Sandro Rogério Ferreira, Karen Spadari Front Cell Infect Microbiol Cellular and Infection Microbiology Toll-like receptors (TLRs) comprise the best-characterized pattern-recognition receptor (PRR) family able to activate distinct immune responses depending on the receptor/adaptor set assembled. TLRs, such as TLR2, TLR4 and TLR9, and their signaling were shown to be important in Paracoccidioides brasiliensis infections. However, the role of the endosomal TLR3 in experimental paracoccidioidomycosys remains obscure. In vitro assays, macrophages of the bone marrow of WT or TLR3(−/−) mice were differentiated for evaluation of their microbicidal activity. In vivo assays, WT or TLR3(−/−) mice were infected intratracheally with Paracoccidioides brasiliensis yeasts for investigation of the lung response type induced. The cytotoxic activity of CD8(+) T cells was assessed by cytotoxicity assay. To confirm the importance of CD8(+) T cells in the control of infection in the absence of tlr3, a depletion assay of these cells was performed. Here, we show for the first time that TLR3 modulate the infection against Paracoccidioides brasiliensis by dampening pro-inflammatory response, NO production, IFN(+)CD8(+)T, and IL-17(+)CD8(+)T cell activation and cytotoxic function, associated with granzyme B and perforin down regulation. As conclusion, we suggest that TLR3 could be used as an escape mechanism of the fungus in an experimental paracoccidioidomycosis. Frontiers Media S.A. 2019-01-10 /pmc/articles/PMC6335947/ /pubmed/30687643 http://dx.doi.org/10.3389/fcimb.2018.00426 Text en Copyright © 2019 Jannuzzi, de Almeida, Amarante-Mendes, Romera, Kaihami, Vasconcelos, Ferreira, de Almeida and Ferreira. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Jannuzzi, Grasielle Pereira
de Almeida, José Roberto Fogaça
Amarante-Mendes, Gustavo P.
Romera, Lavínia Maria Dal'Mas
Kaihami, Gilberto Hideo
Vasconcelos, José Ronnie
Ferreira, Camila Pontes
de Almeida, Sandro Rogério
Ferreira, Karen Spadari
TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title_full TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title_fullStr TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title_full_unstemmed TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title_short TLR3 Is a Negative Regulator of Immune Responses Against Paracoccidioides brasiliensis
title_sort tlr3 is a negative regulator of immune responses against paracoccidioides brasiliensis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335947/
https://www.ncbi.nlm.nih.gov/pubmed/30687643
http://dx.doi.org/10.3389/fcimb.2018.00426
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