Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node
Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node
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DOI：
10.4049/jimmunol.1202283
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发表时间：
2012-12-15
影响因子：
4.4
通讯作者：
Cunningham, Adam F.
中科院分区：
文献类型：
--
作者：
Flores-Langarica, Adriana;Marshall, Jennifer L.;Cunningham, Adam F.
使用蛋白Ag进行全身免疫后，粘膜免疫激活较差。然而，以这种方式诱导粘膜免疫将是克服将Ag递送到这些位点的内在困难的一种有吸引力且简单的方法。来自肠沙门氏菌鼠伤寒血清型 (FliC) 的鞭毛蛋白可显着影响宿主免疫，部分是通过 TLR5 识别来实现的。在这项研究中，我们表明，可溶性 FliC (sFliC) 的全身免疫在腹腔注射后同时在肠系膜淋巴结 (MLN) 和脾脏中驱动不同的免疫反应。和 s.c.免疫接种。在 MLN（而非脾脏）中，sFliC 驱动 TLR5 依赖性 CD103(+) 树突状细胞 (DC) 募集，这与固有层中 CD103(+) DC 数量的减少相关。在 MLN 中，CD103(+) DC 携带 Ag，是内源性和转基因 T 细胞启动的主要引物。 MLN 中与 CD103(+) DC 相互作用的一个关键结果是局部调节性 T 细胞分化的增加。与此同时，全身 sFliC 免疫导致 MLN 中的 FliC 特异性 B 细胞明显转变为 IgA，但其他地方则不然。 TLR5 的缺失对 MLN 的影响比对脾抗体反应的影响更大，这反映在 IgA 血清抗体滴度的降低，但不包括 IgG 的降低。因此，系统性 sFliC 免疫以 CD103(+) DC 为目标，并驱动不同的粘膜 T 和 B 细胞反应。这提供了一种潜在的“特洛伊木马”方法，通过 sFliC 进行系统免疫来调节粘膜免疫。免疫学杂志，2012，189：5745-5754。
Mucosal immunity is poorly activated after systemic immunization with protein Ags. Nevertheless, induction of mucosal immunity in such a manner would be an attractive and simple way to overcome the intrinsic difficulties in delivering Ag to such sites. Flagellin from Salmonella enterica serovar Typhimurium (FliC) can impact markedly on host immunity, in part via its recognition by TLR5. In this study, we show that systemic immunization with soluble FliC (sFliC) drives distinct immune responses concurrently in the mesenteric lymph nodes (MLN) and the spleen after i.p. and s.c. immunization. In the MLN, but not the spleen, sFliC drives a TLR5-dependent recruitment of CD103(+) dendritic cells (DCs), which correlates with a diminution in CD103(+) DC numbers in the lamina propria. In the MLN, CD103(+) DCs carry Ag and are the major primers of endogenous and transgenic T cell priming. A key consequence of these interactions with CD103(+) DCs in the MLN is an increase in local regulatory T cell differentiation. In parallel, systemic sFliC immunization results in a pronounced switching of FliC-specific B cells to IgA in the MLN but not elsewhere. Loss of TLR5 has more impact on MLN than splenic Ab responses, reflected in an ablation of IgA, but not IgG, serum Ab titers. Therefore, systemic sFliC immunization targets CD103(+) DCs and drives distinct mucosal T and B cell responses. This offers a potential "Trojan horse" approach to modulate mucosal immunity by systemically immunizing with sFliC. The Journal of Immunology, 2012, 189: 5745-5754.