Complement Receptor 3 Deficiency Influences Lesion Progression during Leishmania major Infection in BALB/c Mice
Complement Receptor 3 Deficiency Influences Lesion Progression during Leishmania major Infection in BALB/c Mice
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DOI：
10.1128/iai.00802-08
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
McDowell, Mary Ann
中科院分区：
文献类型：
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作者：
Carter, Cristina R.;Whitcomb, James P.;McDowell, Mary Ann
大型利什曼原虫是一种专性细胞内原生动物寄生虫，可引起皮肤利什曼病。与许多细胞内病原体一样，利什曼原虫利用细胞表面受体作为进入宿主细胞的手段。补体受体 3（CR3；也称为 CD11b/CD18）是吞噬细胞上的一种 β(2) 整合素，就是这样的受体之一。 CR3 的连接已被证明可以抑制白细胞介素 12 的产生，白细胞介素 12 是一种细胞因子，对于建立对抗细胞内感染所需的细胞介导反应至关重要。在这里，我们研究了 CR3 在体内皮肤利什曼病的建立和进展中所起的作用。野生型 BALB/c 小鼠的皮肤损伤具有进行性的特点，会导致广泛的组织坏死，同时寄生虫负荷增加；然而，CD11b 缺陷的 BALB/c 小鼠表现出中间表型，其特征是慢性病变和组织损伤发生率降低。感染后进行再感染攻击表明，无论 CD11b 状态如何，易感小鼠 (BALB/c) 和耐药小鼠 (C57BL/6) 都会对硕大利斯特菌产生耐药性。此外，CD11b 不会偏向 T 辅助细胞因子对硕大利斯特菌感染的反应。我们的结果进一步表明，CD11b 对于耐药小鼠的疾病解决并不是必需的；相反，这种蛋白质似乎在易感性中发挥次要作用。
Leishmania major is an obligately intracellular protozoan parasite that causes cutaneous leishmaniasis. Like numerous intracellular pathogens, Leishmania exploits cell surface receptors as a means of entry into host cells. Complement receptor 3 (CR3; also called CD11b/CD18), a beta(2) integrin on phagocytic cells, is one such receptor. Ligation of CR3 has been shown to inhibit the production of interleukin-12, the cytokine that is pivotal in establishing the cell-mediated response necessary to combat intracellular infection. Here we investigate the role that CR3 plays in the establishment and progression of cutaneous leishmaniaisis in vivo. Dermal lesions of wild-type BALB/c mice are characteristically progressive and lead to extensive tissue necrosis coupled with elevated parasite burdens; CD11b-deficient BALB/c mice, however, demonstrate an intermediate phenotype characterized by chronic lesions and a reduced incidence of tissue damage. Infection followed by a reinfection challenge indicates that both susceptible (BALB/c) and resistant (C57BL/6) mice, regardless of CD11b status, develop resistance to L. major. In addition, CD11b does not bias the T helper cytokine response to L. major infection. Our results further indicate that CD11b is not necessary for disease resolution in resistant mice; rather, this protein appears to play a minor role in susceptibility.