Center of Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
PLoS Pathog. 2011 Jan 20;7(1):e1001259. doi: 10.1371/journal.ppat.1001259.
C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of T(H)1 and T(H)-17 cellular responses. Fungal recognition by dectin-1 on human dendritic cells engages the CARD9-Bcl10-Malt1 module to activate NF-κB. Here we demonstrate that Malt1 recruitment is pivotal to T(H)-17 immunity by selective activation of NF-κB subunit c-Rel, which induces expression of T(H)-17-polarizing cytokines IL-1β and IL-23p19. Malt1 inhibition abrogates c-Rel activation and T(H)-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of T(H)-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-κB subunits, dectin-2 selectively activates c-Rel, signifying a specialized T(H)-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive T(H)-17 immunity to fungi via Malt1-dependent activation of c-Rel.
树突状细胞上的 C 型凝集素 dectin-1 和 dectin-2 通过诱导 T(H)1 和 T(H)-17 细胞应答引发针对真菌感染的保护性免疫。树突状细胞上的 dectin-1 对真菌的识别通过 CARD9-Bcl10-Malt1 模块的募集来激活 NF-κB。在这里，我们证明了 Malt1 的募集对于 T(H)-17 免疫至关重要，因为它选择性地激活了 NF-κB 亚基 c-Rel，从而诱导 T(H)-17 极化细胞因子 IL-1β和 IL-23p19 的表达。Malt1 抑制会破坏 c-Rel 的激活和对念珠菌属的 T(H)-17 免疫。我们发现 Malt1 介导的 c-Rel 激活对于 dectin-2 诱导 T(H)-17 极化细胞因子同样是必需的。虽然 dectin-1 激活所有 NF-κB 亚基，但 dectin-2 选择性地激活 c-Rel，这表明 dectin-2 在人类树突状细胞的抗真菌免疫中具有专门的 T(H)-17 增强功能。因此，dectin-1 和 dectin-2 通过 Malt1 依赖性的 c-Rel 激活来控制适应性 T(H)-17 免疫针对真菌。
