Birkner Katharina, Steiner Birte, Rinkler Christina, Kern Yvonne, Aichele Peter, Bogdan Christian, von Loewenich Friederike D
Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
Eur J Immunol. 2008 Dec;38(12):3395-410. doi: 10.1002/eji.200838615.
Anaplasma phagocytophilum is a Gram-negative, obligate intracellular bacterium that exhibits a striking tropism for neutrophils. When we depleted mice of neutrophils, we found that murine susceptibility to anaplasmal infection was dependent on their presence. While serving as sites of bacterial replication, neutrophils do not seem to act as efficient killer cells in A. phagocytophilum infection, because mice deficient for antimicrobial effectors of neutrophils such as myeloperoxidase, granulocyte elastase, and cathepsin G were fully competent in pathogen elimination. To identify components of the immune system other than neutrophils that control A. phagocytophilum, we studied the course of infection in several gene-deficient mouse strains. IFN-gamma production by NK cells was important for initial defense, but not critical for pathogen elimination. In contrast, bacterial clearance was strictly dependent on CD4(+) T cells, but unexpectedly achieved in the absence of perforin, Fas/FasL and major Th1 cytokines such as IL-12, IFN-gamma, and MCP-1. These findings provide a novel paradigm for the control of an intracellular pathogen, which appears to be strikingly different from the CD4(+) T cell-, IL-12-, and IFN-gamma-dependent immunity to other intracellular bacteria.
嗜吞噬细胞无形体是一种革兰氏阴性专性细胞内细菌，对中性粒细胞表现出显著的嗜性。当我们清除小鼠体内的中性粒细胞时，我们发现小鼠对无形体感染的易感性取决于中性粒细胞的存在。虽然中性粒细胞是细菌复制的场所，但在嗜吞噬细胞无形体感染中，它们似乎并不是有效的杀伤细胞，因为缺乏中性粒细胞抗菌效应分子（如髓过氧化物酶、粒细胞弹性蛋白酶和组织蛋白酶G）的小鼠在清除病原体方面完全正常。为了确定除中性粒细胞外控制嗜吞噬细胞无形体的免疫系统成分，我们研究了几种基因缺陷小鼠品系的感染过程。自然杀伤细胞产生的γ干扰素对初始防御很重要，但对病原体清除并不关键。相比之下，细菌清除严格依赖于CD4(+) T细胞，但出乎意料的是，在缺乏穿孔素、Fas/FasL和主要的Th1细胞因子（如白细胞介素-12、γ干扰素和单核细胞趋化蛋白-1）的情况下也能实现细菌清除。这些发现为控制细胞内病原体提供了一种新的模式，这似乎与对其他细胞内细菌的CD4(+) T细胞、白细胞介素-12和γ干扰素依赖性免疫有显著不同。
