title: TLR-4 cooperates with Dectin-1 and mannose receptor to expand Th17 and Tc17 cells induced by Paracoccidioides brasiliensis stimulated dendritic cells.
abstract: 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.
authors: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo, Brazil.
authors: Flávio V
authors: FV
authors: Loures
authors: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo, Brazil.
authors: Eliseu F
authors: EF
authors: Araújo
authors: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo, Brazil.
authors: Claudia
authors: C
authors: Feriotti
authors: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo, Brazil.
authors: Silvia B
authors: SB
authors: Bazan
authors: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo, Brazil.
authors: Vera L G
authors: VL
authors: Calich
keywords: Dectin-1 receptor; Paracoccidioides brasiliensis; Tc17; Th17; innate immunity; mannose receptor; toll-like receptors