1Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Infect Immun. 2011 Jul;79(7):2770-8. doi: 10.1128/IAI.00931-10. Epub 2011 Apr 11.
Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Naïve and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity.
嗜酸性粒细胞和中性粒细胞有助于初级免疫反应中幼虫的杀伤,而中性粒细胞是 Strongyloides stercoralis 感染小鼠次级免疫反应的效应细胞。本研究的目的是确定嗜酸性粒细胞和中性粒细胞用于控制 Strongyloides stercoralis 感染的分子机制。使用缺乏嗜酸性粒细胞颗粒产物主要碱性蛋白 (MBP) 和嗜酸性过氧化物酶 (EPO) 的小鼠,确定如果不存在其他效应细胞,嗜酸性粒细胞通过初级免疫反应中的 MBP 依赖性机制杀死幼虫。用 S. stercoralis 感染 PHIL 小鼠(缺乏嗜酸性粒细胞)导致初级和次级免疫反应的发展类似于野生型小鼠,这表明嗜酸性粒细胞不是幼虫杀伤或次级免疫发展的绝对要求。用中性粒细胞耗竭抗体处理 PHIL 小鼠导致幼虫杀伤显著受损。用髓过氧化物酶 (MPO) 缺乏的中性粒细胞感染 S. stercoralis 的 naive 和免疫小鼠的幼虫杀伤明显减少。结论是,初级免疫反应存在冗余,嗜酸性粒细胞通过 MBP 依赖性机制杀死幼虫,而中性粒细胞通过 MPO 依赖性机制杀死蠕虫。嗜酸性粒细胞对于次级免疫的发展或功能不是必需的,但中性粒细胞的 MPO 对于保护性次级免疫是必需的。