Central role for B lymphocytes and CD4+ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium
Central role for B lymphocytes and CD4+ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium
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DOI：
10.1128/iai.71.9.5077-5086.2003
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发表时间：
2003-09-01
影响因子：
3.1
通讯作者：
Dougan, G
中科院分区：
文献类型：
--
作者：
Simmons, CP;Clare, S;Dougan, G
轮状柠檬酸杆菌是一种附着消失的细菌病原体，它能引起小鼠结肠上皮的急性感染，并在免疫能力强的小鼠中引起轻度结肠炎。本研究描述了T细胞亚群和B淋巴细胞在轮状病毒免疫中的作用。C57BL/6小鼠经口感染轮状芽胞杆菌后，感染在3~4周内消失。相反，口服感染轮状芽胞杆菌的RAG1(-/-)小鼠的全身和结肠组织含有高和持续的病原体负荷，在结肠中这会导致严重的结肠炎。缺乏CD4(+)T细胞而不是CD8(+)T细胞的C57BL/6小鼠对感染高度敏感，也会患上严重的结肠炎。尽管病原体负担大大增加，但耗尽CD4(+)T细胞的小鼠对轮状芽胞杆菌毒力相关的两个决定因素EspA和Instin的免疫球蛋白G(IgG)和IgA抗体反应也减弱。T细胞室完整但缺乏B细胞的小鼠(木乃伊小鼠)，对轮状芽胞杆菌感染高度敏感。通过将恢复期的免疫血清过继转移给感染的MUMA小鼠，可以恢复全身免疫，但不能恢复粘膜免疫。过继转移免疫B细胞，而不是幼稚B细胞，为受体MUMA小鼠提供了高度可变的免疫。结果表明，B细胞介导的免疫反应是解决轮状芽胞杆菌感染的关键，但发生这种情况的机制需要进一步研究。这些数据与了解人类对肠道附着和清除细菌病原体的免疫力有关。
Citrobacter rodentium, an attaching-effacing bacterial pathogen, establishes an acute infection of the murine colonic epithelium and induces a mild colitis in immunocompetent mice. This study describes the role of T-cell subsets and B lymphocytes in immunity to C rodentium. C57Bl/6 mice orally infected with C. rodentium resolved infection within 3 to 4 weeks. Conversely, systemic and colonic tissues of RAG1(-/-) mice orally infected with C. rodentium contained high and sustained pathogen loads, and in the colon this resulted in a severe colitis. C57Bl/6 mice depleted of CD4(+) T cells, but not CD8(+) T cells, were highly susceptible to infection and also developed severe colitis. Mice depleted of CD4(+) T cells also had diminished immunoglobulin G (IgG) and IgA antibody responses to two C. rodentium virulence-associated determinants, i.e., EspA and intimin, despite having a massively increased pathogen burden. Mice with an intact T-cell compartment, but lacking B cells (muMT mice), were highly susceptible to C. rodentium infection. Systemic immunity, but not mucosal immunity, could be restored by adoptive transfer of convalescent immune sera to infected muMT mice. Adoptive transfer of immune B cells, but not naive B cells, provided highly variable immunity to recipient muMT mice. The results suggest that B-cell-mediated immune responses are central to resolution of a C. rodentium infection but that the mechanism through which this occurs requires further investigation. These data are relevant to understanding immunity to enteric attaching and effacing bacterial pathogens of humans.