Prado Acosta Mariano, Goyette-Desjardins Guillaume, Scheffel Jörg, Dudeck Anne, Ruland Jürgen, Lepenies Bernd
Research Center for Emerging Infections and Zoonoses, Institute for Immunology, University of Veterinary Medicine, Hannover, Germany.
Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
Front Immunol. 2021 Mar 1;12:602067. doi: 10.3389/fimmu.2021.602067. eCollection 2021.
C-type lectin receptors (CLRs) are pattern recognition receptors that are crucial in the innate immune response. The gastrointestinal tract contributes significantly to the maintenance of immune homeostasis; it is the shelter for billions of microorganisms including many genera of sp. Previously, it was shown that host-CLR interactions with gut microbiota play a crucial role in this context. The Macrophage-inducible C-type lectin (Mincle) is a Syk-coupled CLR that contributes to sensing of mucosa-associated commensals. In this study, we identified Mincle as a receptor for the Surface (S)-layer of the probiotic bacteria modulating GM-CSF bone marrow-derived cells (BMDCs) functions. We found that the S-layer/Mincle interaction led to a balanced cytokine response in BMDCs by triggering the release of both pro- and anti-inflammatory cytokines. In contrast, BMDCs derived from Mincle, CARD9 or conditional Syk mice failed to maintain this balance, thus leading to an increased production of the pro-inflammatory cytokines TNF and IL-6, whereas the levels of the anti-inflammatory cytokines IL-10 and TGF-β were markedly decreased. Importantly, this was accompanied by an altered CD4 T cell priming capacity of Mincle BMDCs resulting in an increased CD4 T cell IFN-γ production upon stimulation with S-layer. Our results contribute to the understanding of how commensal bacteria regulate antigen-presenting cell (APC) functions and highlight the importance of the Mincle/Syk/Card9 axis in APCs as a key factor in host-microbiota interactions.
C型凝集素受体（CLRs）是模式识别受体，在先天免疫反应中起关键作用。胃肠道对维持免疫稳态有重要贡献；它是数十亿微生物的庇护所，包括许多属的物种。此前研究表明，宿主CLR与肠道微生物群的相互作用在此过程中起关键作用。巨噬细胞诱导性C型凝集素（Mincle）是一种与Syk偶联的CLR，有助于感知黏膜相关共生菌。在本研究中，我们将Mincle鉴定为益生菌表面（S）层的受体，其可调节粒细胞-巨噬细胞集落刺激因子骨髓来源细胞（BMDCs）的功能。我们发现S层/Mincle相互作用通过触发促炎和抗炎细胞因子的释放，导致BMDCs中细胞因子反应平衡。相比之下，源自Mincle、CARD9或条件性Syk小鼠的BMDCs无法维持这种平衡，从而导致促炎细胞因子TNF和IL-6的产生增加，而抗炎细胞因子IL-10和TGF-β的水平则显著降低。重要的是，这伴随着Mincle BMDCs的CD4 T细胞启动能力改变，导致在用S层刺激后CD4 T细胞IFN-γ产生增加。我们的研究结果有助于理解共生细菌如何调节抗原呈递细胞（APC）的功能，并强调Mincle/Syk/Card9轴在APC中作为宿主-微生物群相互作用关键因素的重要性。
