Lysosomal phospholipase A2: A novel player in host immunity to Mycobacterium tuberculosis
Lysosomal phospholipase A2: A novel player in host immunity to Mycobacterium tuberculosis
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DOI：
10.1002/eji.201344383
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发表时间：
2014-06
影响因子：
5.4
通讯作者：
B. Schneider;J. Behrends;K. Hagens;N. Harmel;J. Shayman;U. Schaible
中科院分区：
文献类型：
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作者：
B. Schneider;J. Behrends;K. Hagens;N. Harmel;J. Shayman;U. Schaible
磷脂酶催化膜磷脂裂解成较小的生物活性分子。溶酶体磷脂酶 A2 (LPLA2) 在巨噬细胞中特异性表达。小鼠体内 LPLA2 基因缺失会导致组织巨噬细胞中溶酶体磷脂积累，从而导致磷脂沉积症。这种表型在肺泡巨噬细胞中最为突出，其中 LPLA2 有助于表面活性剂磷脂的降解。肺泡巨噬细胞中 LPLA2 的高表达促使我们研究其在宿主针对呼吸道病原体结核分枝杆菌（结核病病原体）免疫中的作用。在这里，我们报告说，LPLA2 缺陷小鼠对结核分枝杆菌的适应性免疫反应受损。在气溶胶感染结核分枝杆菌后，LPLA2缺陷小鼠表现出分枝杆菌计数增加，但肺部免疫病理学和肺部炎症反应减少。淋巴结中 T 细胞启动受损与肺 T 细胞招募和激活受损有关。加上 Th1 型细胞因子产生的减少，这些结果表明 LPLA2 对于诱导针对结核分枝杆菌的适应性 T 细胞免疫是不可或缺的。综上所述，我们发现了溶酶体磷脂降解酶的一种意想不到的新颖功能。
Phospholipases catalyze the cleavage of membrane phospholipids into smaller bioactive molecules. The lysosomal phospholipase A2 (LPLA2) is specifically expressed in macrophages. LPLA2 gene deletion in mice causes lysosomal phospholipid accumulation in tissue macrophages leading to phospholipidosis. This phenotype becomes most prominent in alveolar macrophages where LPLA2 contributes to surfactant phospholipid degradation. High expression of LPLA2 in alveolar macrophages prompted us to investigate its role in host immunity against the respiratory pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we report that adaptive immune responses to M. tuberculosis were impaired in LPLA2 deficient mice. Upon aerosol infection with M. tuberculosis, LPLA2 deficient mice showed enhanced mycobacterial counts but less lung immunopathology and pulmonary inflammatory responses. Compromised T‐cell priming in the lymph nodes was associated with impaired pulmonary T‐cell recruitment and activation. Together with reduced Th1 type cytokine production, these results indicate that LPLA2 is indispensable for the induction of adaptive T‐cell immunity to M. tuberculosis. Taken together, we identified an unexpected and novel function of a lysosomal phospholipid‐degrading enzyme.