Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis
Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis
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DOI：
10.1126/science.aat4042
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发表时间：
2019-03-08
期刊：
影响因子：
56.9
通讯作者：
Ivanov, Ivaylo I.
中科院分区：
文献类型：
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作者：
Ladinsky, Mark S.;Araujo, Leandro P.;Ivanov, Ivaylo I.
共生细菌影响宿主生理，但不入侵宿主组织。我们发现，从分段丝状细菌（SFB）的蛋白质转移到肠上皮细胞（IEC）通过粘附定向的内吞作用，这是不同于网格蛋白依赖的内吞作用的侵入性病原体。该过程以细胞分裂控制蛋白42同源物（CDC 42）依赖性方式将微生物细胞壁相关蛋白（包括刺激粘膜T辅助17（TH 17）细胞分化的抗原）转移到IEC的胞质溶胶中。在体内去除CDC42活性导致由SFB诱导的内吞作用的破坏和上皮抗原获得的减少，从而导致粘膜TH17细胞的损失。我们的研究结果证明了常驻肠道微生物与宿主之间的直接交流，并表明在生理条件下，IEC从肠道细菌中获得抗原，以产生对常驻微生物群的T细胞反应。
Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall-associated proteins, including an antigen that stimulates mucosal T helper 17 (TH17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)-dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal TH17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.