Production of IFN-γ by CD4 T cells is essential for resolving ehrlichia infection
Production of IFN-γ by CD4 T cells is essential for resolving ehrlichia infection
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DOI：
10.4049/jimmunol.172.11.6894
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Winslow, G
中科院分区：
文献类型：
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作者：
Bitsaktsis, C;Huntington, J;Winslow, G
为了说明细胞免疫在埃立克体感染过程中的作用，我们使用了一种新描述的单核细胞埃立克体病模型，该模型是由从卵形硬蜱中分离的埃立克体感染小鼠引起的。免疫活性C57 BL/6和BALB/c小鼠对IOE感染表现出剂量依赖性易感性。感染高剂量接种物（类似于1000个微生物）的小鼠在感染后12天内表现出明显的血小板减少、淋巴细胞减少、贫血和发病率。感染与许多组织的细菌定植有关。相反，用低剂量接种物（类似于100个微生物）感染的小鼠仅表现出短暂的疾病，并且能够解决感染。SCID小鼠对低剂量感染高度敏感，表明需要获得性免疫。C57 BL/6和BALB/c小鼠对亚致死性攻击的抵抗是CD 4依赖性的，而不是CD 8依赖性的，需要IL-12 p40依赖性细胞因子、IFN-γ和TNF-α，而不是IL-4。从感染小鼠纯化的CD 4 T细胞在体外响应IOE Ag增殖。T细胞增殖与IFN-γ的产生有关，CD 4 T细胞产生的这种细胞因子使IFN-γ缺陷小鼠免于致命感染。外源性IFN-γ能够在感染的巨噬细胞中诱导杀微生物活性。这些数据表明，涉及CD 4细胞和I型细胞因子的经典免疫机制负责巨噬细胞活化和消除这种细胞内细菌病原体。
To address the role of cellular immunity during ehrlichia infection, we have used a newly described model of monocytic ehrlichiosis that results from infection of mice by an ehrlichia that was isolated from an Ixodes ovatus tick (Ixodes ovatus ehrlichia, IOE). Immunocompetent C57BL/6 and BALB/c mice exhibited a dose-dependent susceptibility to IOE infection. Mice infected with a high dose inoculum (similar to1000 organisms) exhibited pronounced thrombocytopenia, lymphopenia, anemia, and morbidity within 12 days postinfection. Infection was associated with bacterial colonization of a number of tissues. In contrast, mice infected with a low dose inoculum (similar to100 organisms) exhibited only transient disease and were able to resolve the infection. SCID mice were highly susceptible to low-dose infection, indicating that adaptive immunity was required. Resistance to sublethal challenge in both C57BL/6 and BALB/c mice was CD4-, but not CD8-, dependent and required IL-12p40-dependent cytokines, IFN-gamma, and TNF-alpha, but not IL-4. CD4 T cells purified from infected mice proliferated in vitro in response to IOE Ags. T cell proliferation was associated with production of IFN-gamma, and the production of this cytokine by CD4 T cells rescued IFN-gamma-deficient mice from fatal infection. Exogenous IFN-gamma was capable of inducing microbiocidal activity in infected macrophages. The data suggest that classical immune mechanisms involving CD4 cells and type I cytokines are responsible for macrophage activation and for elimination of this intracellular bacterial pathogen.