%A Loures,Flávio V.
%A Araújo,Eliseu F.
%A Feriotti,Claudia
%A Bazan,Silvia B.
%A Calich,Vera L. G.
%D 2015
%J Frontiers in Microbiology
%C
%F
%G English
%K Paracoccidioides brasiliensis,innate immunity,Toll-Like Receptors,Mannose receptor,Dectin-1 Receptor,Th17,Tc17.
%Q
%R 10.3389/fmicb.2015.00261
%W
%L
%M
%P
%7
%8 2015-March-31
%9 Original Research
%+ Prof Vera L. G. Calich,Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo,São Paulo, Brazil,vlcalich@icb.usp.br
%#
%! PRRs,Th17/Tc17 cells in paracoccidioidomycosis
%*
%<
%T TLR-4 cooperates with Dectin-1 and mannose receptor to expand Th17 and Tc17 cells induced by Paracoccidioides brasiliensis stimulated dendritic cells
%U https://www.frontiersin.org/articles/10.3389/fmicb.2015.00261
%V 6
%0 JOURNAL ARTICLE
%@ 1664-302X
%X The concomitant use of diverse pattern recognition receptors (PRRs) by innate immune cells can result in synergistic or inhibitory activities that profoundly influence anti-microbial immunity. Dectin-1 and the mannose receptor (MR) are C-type lectin receptors (CLRs) previously reported to cooperate with toll-like receptors (TLRs) signaling in the initial inflammatory response and in the induction of adaptive Th17 and Tc17 immunity mediated by CD4+ and CD8+ T cells, respectively. The protective immunity against paracoccidioidomycosis, the most prevalent fungal infection of Latin America, was previously shown to be influenced by these T cell subsets motivating us to study the contribution of TLRs, Dectin-1, and MR to the development of Th17/Tc17 immunity. First, curdlan a specific Dectin-1 agonist was used to characterize the influence of this receptor in the proliferative response and Th17/Tc17 differentiation of naïve lymphocytes induced by Paracoccidioides brasiliensis activated dendritic cells (DCs) from C57BL/6 mice. Then, wild type (WT), Dectin-1–/–, TLR-2–/–, and TLR-4–/– DCs treated or untreated with anti-Dectin-1 and anti-MR antibodies were used to investigate the contribution of these receptors in lymphocyte activation and differentiation. We verified that curdlan induces an enhanced lymphocyte proliferation and development of IL-17 producing CD4+ and CD8+ T cells. In addition, treatment of WT, TLR-2–/–, and TLR-4–/– DCs by anti-Dectin-1 antibodies or antigen presentation by Dectin-1–/– DCs led to decreased lymphoproliferation and impaired Th17 and Tc17 expansion. These responses were also inhibited by anti-MR treatment of DCs, but a synergistic action on Th17/Tc17 differentiation was mediated by TLR-4 and MR. Taken together, our results indicate that diverse TLRs and CLRs are involved in the induction of lymphocyte proliferation and Th17/Tc17 differentiation mediated by P. brasiliensis activated DCs, but a synergist action was restricted to Dectin-1, TLR-4, and MR.