Department of Entomology and Center for Disease Vector Research, University of California-Riverside, Riverside, California, USA.
Infect Immun. 2012 Sep;80(9):3194-205. doi: 10.1128/IAI.00532-12. Epub 2012 Jul 2.
Anaplasma phagocytophilum is a tick-borne rickettsial pathogen that provokes an acute inflammatory response during mammalian infection. The illness caused by A. phagocytophilum, human granulocytic anaplasmosis, occurs irrespective of pathogen load and results instead from host-derived immunopathology. Thus, characterizing A. phagocytophilum genes that affect the inflammatory process is critical for understanding disease etiology. By using an A. phagocytophilum Himar1 transposon mutant library, we showed that a single transposon insertion into the A. phagocytophilum dihydrolipoamide dehydrogenase 1 gene (lpda1 [APH_0065]) affects inflammation during infection. A. phagocytophilum lacking lpda1 revealed enlargement of the spleen, increased splenic extramedullary hematopoiesis, and altered clinicopathological abnormalities during mammalian colonization. Furthermore, LPDA1-derived immunopathology was independent of neutrophil infection and correlated with enhanced reactive oxygen species from NADPH oxidase and nuclear factor (NF)-κB signaling in macrophages. Taken together, these findings suggest the presence of different signaling pathways in neutrophils and macrophages during A. phagocytophilum invasion and highlight the importance of LPDA1 as an immunopathological molecule.
嗜吞噬细胞无形体是一种蜱传立克次体病原体，在哺乳动物感染期间会引发急性炎症反应。由嗜吞噬细胞无形体引起的疾病，即人类粒细胞无形体病，与病原体载量无关，而是由宿主免疫病理学引起的。因此，鉴定影响炎症过程的嗜吞噬细胞无形体基因对于理解疾病病因至关重要。通过使用嗜吞噬细胞无形体 Himar1 转座子突变体文库，我们表明单个转座子插入到嗜吞噬细胞无形体二氢硫辛酰胺脱氢酶 1 基因（lpda1 [APH_0065]）中会影响感染期间的炎症反应。缺乏 lpda1 的嗜吞噬细胞无形体显示脾脏肿大、脾脏外骨髓造血增加，并在哺乳动物定植期间改变临床病理异常。此外，LPDA1 引起的免疫病理学与中性粒细胞感染无关，并且与巨噬细胞中 NADPH 氧化酶和核因子 (NF)-κB 信号转导产生的活性氧物质增强相关。总之，这些发现表明在嗜吞噬细胞无形体入侵期间，中性粒细胞和巨噬细胞中存在不同的信号通路，并强调 LPDA1 作为免疫病理分子的重要性。
