A complex immune response to flagellin epitope variation in commensal communities
A complex immune response to flagellin epitope variation in commensal communities
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DOI：
10.1016/j.chom.2021.02.006
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发表时间：
2021-04-14
影响因子：
30.3
通讯作者：
Dangl, Jeffery L.
中科院分区：
文献类型：
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作者：
Colaianni, Nicholas R.;Parys, Katarzyna;Dangl, Jeffery L.
免疫系统通过识别称为微生物相关分子模式（MAMP）的“非自身”分子来限制微生物病原体。目前还不清楚免疫应答是如何调节到或通过肠道微生物群中存在的MAMP多样性调节的。我们系统地研究了鞭毛蛋白（flg22），一个MAMP植物检测的肽衍生物的变异性。我们定义了实质性的功能多样性。大多数flg22肽逃避识别，而其他肽通过拮抗和信号调节操纵免疫而有助于逃避。我们建立了一个信号整合的范例，其中鞭毛蛋白受体的连续信号输出是可分离的，并允许由鞭毛衍生的flg22表位变体进行重编程。植物相关群落富集免疫逃避flg22表位，但在抑制免疫系统的生理应激下，免疫活化flg22表位变得富集。免疫操纵表位的存在表明，它们进化为沟通或利用免疫系统进行宿主定殖，因此可以影响肠道微生物群的组成。
Immune systems restrict microbial pathogens by identifying "non-self'' molecules called microbe-associated molecular patterns (MAMPs). It is unclear how immune responses are tuned to or by MAMP diversity present in commensal microbiota. We systematically studied the variability of commensal peptide derivatives of flagellin (flg22), a MAMP detected by plants. We define substantial functional diversity. Most flg22 peptides evade recognition, while others contribute to evasion by manipulating immunity through antagonism and signal modulation. We establish a paradigm of signal integration, wherein the sequential signaling outputs of the flagellin receptor are separable and allow for reprogramming by commensal-derived flg22 epitope variants. Plant-associated communities are enriched for immune evading flg22 epitopes, but upon physiological stress that represses the immune system, immune-activating flg22 epitopes become enriched. The existence of immune-manipulating epitopes suggests that they evolved to either communicate or utilize the immune system for host colonization and thus can influence commensal microbiota community composition.