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.