CHU de Québec-Université Laval Research Center, Department of Microbiology, Infectiology and Immunology, Quebec City, Quebec, Canada.
ARThrite Research Center, University Laval, Quebec City, Quebec, Canada.
JCI Insight. 2022 Jan 25;7(2):e152638. doi: 10.1172/jci.insight.152638.
Secreted phospholipase A2-IIA (sPLA2-IIA) hydrolyzes phospholipids to liberate lysophospholipids and fatty acids. Given its poor activity toward eukaryotic cell membranes, its role in the generation of proinflammatory lipid mediators is unclear. Conversely, sPLA2-IIA efficiently hydrolyzes bacterial membranes. Here, we show that sPLA2-IIA affects the immune system by acting on the intestinal microbial flora. Using mice overexpressing transgene-driven human sPLA2-IIA, we found that the intestinal microbiota was critical for both induction of an immune phenotype and promotion of inflammatory arthritis. The expression of sPLA2-IIA led to alterations of the intestinal microbiota composition, but housing in a more stringent pathogen-free facility revealed that its expression could affect the immune system in the absence of changes to the composition of this flora. In contrast, untargeted lipidomic analysis focusing on bacteria-derived lipid mediators revealed that sPLA2-IIA could profoundly alter the fecal lipidome. The data suggest that a singular protein, sPLA2-IIA, produces systemic effects on the immune system through its activity on the microbiota and its lipidome.
分泌型磷脂酶 A2-IIA（sPLA2-IIA）水解磷脂以释放溶血磷脂和脂肪酸。鉴于其对真核细胞膜的活性较差，其在产生促炎脂质介质中的作用尚不清楚。相反，sPLA2-IIA 能有效地水解细菌膜。在这里，我们表明 sPLA2-IIA 通过作用于肠道微生物菌群来影响免疫系统。使用过表达转基因驱动的人 sPLA2-IIA 的小鼠，我们发现肠道微生物群对于诱导免疫表型和促进炎症性关节炎都是至关重要的。sPLA2-IIA 的表达导致肠道微生物群组成的改变，但在更严格的无病原体设施中饲养表明，其表达可以影响免疫系统，而无需改变这种菌群的组成。相比之下，针对细菌衍生的脂质介质的非靶向脂质组学分析表明，sPLA2-IIA 可以深刻地改变粪便脂质组。这些数据表明，单一蛋白 sPLA2-IIA 通过其对微生物组及其脂质组的活性对免疫系统产生全身效应。
