Background Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. Aim We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. Methods Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium. Results SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. Conclusions SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

中文翻译：

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肠道共生微生物用先天受体 SLAMF4 印记肠道免疫细胞，这有助于肠道免疫保护抵抗肠道病原体

背景宿主免疫细胞和肠道微生物群之间的相互作用对于肠道的完整性和功能至关重要。这些相互作用如何调节肠道中的免疫细胞反应仍然是该领域的一个主要空白。目的 我们已经鉴定出信号淋巴细胞活化分子家族成员 4 (SLAMF4) 作为肠道免疫的免疫调节剂。目的是确定 SLAMF4 如何在肠道中获得以及它对肠道免疫的贡献是什么。方法在小鼠和人类中评估SLAMF4的表达。使用GFPtg骨髓嵌合体小鼠、淋巴毒素α和TNLG8A缺陷小鼠以及无菌小鼠研究诱导机制。使用单核细胞增生李斯特菌和啮齿动物细胞杆菌的口腔感染揭示了免疫保护中的作用。结果 SLAMF4 是小鼠和人类肠道免疫细胞的选择性标记物。SLAMF4 诱导直接发生在肠黏膜中，不涉及肠道相关淋巴组织。肠道细菌产物，尤其是肠道厌氧菌产物和肠道常驻抗原呈递细胞 (APC) TNLG8A 是肠道 SLAMF4 诱导的关键贡献者。重要的是，缺乏 SLAMF4 表达导致小鼠对口腔病原体感染的易感性增加，最终导致它们过早死亡。结论 SLAMF4 是肠道免疫细胞的标志物，有助于抵御肠道病原体，其表达取决于肠道微生物群的存在。