Mikulic Josip, Longet Stéphanie, Favre Laurent, Benyacoub Jalil, Corthesy Blaise
R&D Laboratory, Division of Immunology and Allergy, CHUV, Centre des Laboratoires d'Epalinges, 1066 Epalinges, Switzerland.
Nutrition and Health, Nestlé Research Center, 1000 Lausanne 26, Switzerland.
Cell Mol Immunol. 2017 Jun;14(6):546-556. doi: 10.1038/cmi.2015.110. Epub 2016 Mar 14.
The importance of secretory IgA in controlling the microbiota is well known, yet how the antibody affects the perception of the commensals by the local immune system is still poorly defined. We have previously shown that the transport of secretory IgA in complex with bacteria across intestinal microfold cells results in an association with dendritic cells in Peyer's patches. However, the consequences of such an interaction on dendritic cell conditioning have not been elucidated. In this study, we analyzed the impact of the commensal Lactobacillus rhamnosus, alone or associated with secretory IgA, on the responsiveness of dendritic cells freshly recovered from mouse Peyer's patches, mesenteric lymph nodes, and spleen. Lactobacillus rhamnosus-conditioned mucosal dendritic cells are characterized by increased expression of Toll-like receptor regulatory proteins [including single immunoglobulin interleukin-1 receptor-related molecule, suppressor of cytokine signaling 1, and Toll-interacting molecule] and retinaldehyde dehydrogenase 2, low surface expression of co-stimulatory markers, high anti- versus pro-inflammatory cytokine production ratios, and induction of T regulatory cells with suppressive function. Association with secretory IgA enhanced the anti-inflammatory/regulatory Lactobacillus rhamnosus-induced conditioning of mucosal dendritic cells, particularly in Peyer's patches. At the systemic level, activation of splenic dendritic cells exposed to Lactobacillus rhamnosus was partially dampened upon association with secretory IgA. These data suggest that secretory IgA, through coating of commensal bacteria, contributes to the conditioning of mucosal dendritic cells toward tolerogenic profiles essential for the maintenance of intestinal homeostasis.
分泌型IgA在控制微生物群方面的重要性已广为人知，但这种抗体如何影响局部免疫系统对共生菌的识别仍不清楚。我们之前已经表明，与细菌结合的分泌型IgA跨肠道微褶细胞转运后会与派尔集合淋巴结中的树突状细胞发生关联。然而，这种相互作用对树突状细胞调节的影响尚未阐明。在本研究中，我们分析了共生鼠李糖乳杆菌单独或与分泌型IgA结合时，对从小鼠派尔集合淋巴结、肠系膜淋巴结和脾脏中新鲜分离的树突状细胞反应性的影响。经鼠李糖乳杆菌调节的黏膜树突状细胞的特征是Toll样受体调节蛋白[包括单免疫球蛋白白细胞介素-1受体相关分子、细胞因子信号传导抑制因子1和Toll相互作用分子]和视黄醛脱氢酶2的表达增加，共刺激标志物的表面表达较低，抗炎与促炎细胞因子产生比例较高，以及诱导具有抑制功能的调节性T细胞。与分泌型IgA结合增强了鼠李糖乳杆菌诱导的黏膜树突状细胞的抗炎/调节性调节，尤其是在派尔集合淋巴结中。在全身水平，与分泌型IgA结合后，暴露于鼠李糖乳杆菌的脾树突状细胞的激活受到部分抑制。这些数据表明，分泌型IgA通过包裹共生细菌，有助于将黏膜树突状细胞调节为维持肠道稳态所必需的致耐受性表型。
