TLR-4 cooperates with Dectin-1 and mannose receptor to expand Th17 and Tc17 cells induced by Paracoccidioides brasiliensis stimulated dendritic cells

Autor(es)

Loures, Flavio V. ^[1] ; Araujo, Eliseu F. ^[1] ; Feriotti, Claudia ^[1] ; Bazan, Silvia B. ^[1] ; Calich, Vera L. G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 6, MAR 31 2015.
• Citações Web of Science: 24

Resumo

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 naive 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. (AU)

• Processo FAPESP: 10/52275-5 - Influência dos receptores de imunidade inata (TLR2, TLR4 e Dectina-1) no comportamento de células dendríticas e na determinação do padrão de imunidade adaptativa dos hospedeiros contra o paracocciodióides
• Beneficiário: Vera Lucia Garcia Calich
• Modalidade de apoio: Auxílio à Pesquisa - Regular