Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.
Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.
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DOI：
10.1038/mi.2017.43
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发表时间：
2018-01
影响因子：
8
通讯作者：
Mizgerd JP
中科院分区：
文献类型：
--
作者：
Smith NM;Wasserman GA;Coleman FT;Hilliard KL;Yamamoto K;Lipsitz E;Malley R;Dooms H;Jones MR;Quinton LJ;Mizgerd JP
随着儿童年龄的增长，他们对引起肺炎的各种微生物变得不那么敏感。这些微生物是致病菌，在儿童时期多次感染呼吸道，产生免疫记忆。为了阐明这种天然获得性免疫保护对肺炎的机制，我们通过用不匹配的肺炎链球菌（肺炎球菌）血清型感染小鼠的气道来模拟小鼠的相关免疫史。先前的肺炎球菌感染提供了对异型、高毒力肺炎球菌的保护，如细菌负荷减少和长期灭菌免疫所证明的。这种保护作用在最终感染前因CD 4+细胞耗竭而减弱。先前肺炎球菌感染的消退在肺中接种了CD 4+驻留记忆T（TRM）细胞，其通过产生多种效应细胞因子（特别是IL-17 A）来响应异型肺炎球菌刺激。大叶性肺炎后，产生IL-17的CD 4 + TRM细胞局限于先前感染的肺叶，而不是分散在整个下呼吸道。重要的是，肺炎保护作用也仅限于免疫经历的肺叶。因此，区域定位的记忆细胞提供上级由系统或中枢记忆免疫防御介导的局部组织保护。我们的结论是，呼吸道细菌感染引起的CD 4 + TRM细胞填补了局部生态位，以优化受影响组织的异型保护，预防肺炎。
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally-acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4+ cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4+ resident memory T (TRM) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly IL-17A. Following lobar pneumonias, IL-17-producing CD4+ TRM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically-experienced lobe. Thus, regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4+ TRM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.
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