Toll‐like receptor 5 is not essential for the promotion of secretory immunoglobulin A antibody responses to flagellated bacteria
Toll‐like receptor 5 is not essential for the promotion of secretory immunoglobulin A antibody responses to flagellated bacteria
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Toll样受体5对于促进分泌性免疫球蛋白A抗体对有鞭毛细菌的反应不是必需的
DOI：
10.1111/1348-0421.12336
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发表时间：
2015
影响因子：
2.6
通讯作者：
Masafumi Yamamoto
中科院分区：
文献类型：
--
作者：
T. Hashizume;Masafumi Yamamoto
Toll样受体5识别细菌鞭毛蛋白，在先天免疫中起关键作用，并有助于鞭毛蛋白特异性体液免疫。此外，表达TLR 5的树突状细胞在肠道伊加合成中发挥重要作用;然而，TLR 5对抗原（Ag）特异性粘膜免疫的贡献仍不清楚。因此，本研究探讨了TLR 5是否是诱导肠道分泌型（S）伊加抗体（Ab）对鞭毛蛋白和附着在细菌表面的细菌抗原的应答所必需的。我们的研究结果表明，当TLR 5敲除（TLR 5 −/−）小鼠口服免疫表达破伤风毒素C片段的重组沙门氏菌（rSalmonella‐Tox C）时，破伤风类毒素（TT）和鞭毛蛋白（FliC）特异性全身IgG和肠道SIgA抗体被引发。TLR 5 −/−小鼠脾脏中TT特异性IgG抗体形成细胞（AFC）和固有层（LP）中伊加AFC的数量与野生型小鼠相当。rSalmonella‐Tox C在TLR 5 −/−小鼠、缺乏派伊尔集合淋巴结（PP）的TLR 5 −/−小鼠和野生型小鼠中传播相同。相比之下，TLR 5 −/− PP-null小鼠未能在肠道中诱导TT-和FliC-特异性SIgA Ab，并且在LP中显示TT-特异性伊加AFC的数量显著减少。这些结果表明，TLR 5是诱导鞭毛蛋白和表面抗原特异性的全身和粘膜免疫对口腔鞭毛细菌。相反，发生在PP中的病原体识别是诱导针对鞭毛细菌的粘膜免疫的先决条件。
Toll‐like receptor 5 recognizes bacterial flagellin, plays a critical role in innate immunity, and contributes to flagellin‐specific humoral immunity. Further, TLR5‐expressing dendritic cells play an important role in IgA synthesis in the intestine; however, the contribution of TLR5 to antigen (Ag)‐specific mucosal immunity remains unclear. Thus, whether TLR5 is essential for the induction of intestinal secretory (S)IgA antibody (Ab) responses against flagellin and bacterial Ags attached to the bacterial surface in response to an oral flagellated bacterium, Salmonella, was explored in this study. Our results indicate that when TLR5 knockout (TLR5−/−) mice are orally immunized with recombinant Salmonella expressing fragment C of tetanus toxin (rSalmonella‐Tox C), tetanus toxoid (TT)‐ and flagellin (FliC)‐specific systemic IgG and intestinal SIgA Abs are elicited. The numbers of TT‐specific IgG Ab‐forming cells (AFCs) in the spleen and IgA AFCs in the lamina propria (LP) of TLR5−/− mice were comparable to those in wild‐type mice. rSalmonella‐Tox C was equally disseminated in TLR5−/− mice, TLR5−/− mice lacking Peyer's patches (PPs), and wild‐type mice. In contrast, TLR5−/− PP‐null mice failed to induce TT‐ and FliC‐specific SIgA Abs in the intestine and showed significantly reduced numbers of TT‐specific IgA AFCs in the LP. These results suggest that TLR5 is dispensable for the induction of flagellin and surface Ag‐specific systemic and mucosal immunity against oral flagellated bacteria. Rather, pathogen recognition, which occurs in PPs, is a prerequisite for the induction of mucosal immunity against flagellated bacteria.
影响因子：
30.5
作者：
Uematsu, Satoshi;Jang, Myoung Ho;Akira, Shizuo
通讯作者：
Akira, Shizuo