The interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.

TitleThe interaction of secreted phospholipase A2-IIA with the microbiota alters its lipidome and promotes inflammation.
Publication TypeJournal Article
Year of Publication2022
AuthorsDoré, E, Joly-Beauparlant, C, Morozumi, S, Mathieu, A, Lévesque, T, Allaeys, I, Duchez, A-C, Cloutier, N, Leclercq, M, Bodein, A, Payré, C, Martin, C, Petit-Paitel, A, Gelb, MH, Rangachari, M, Murakami, M, Davidovic, L, Flamand, N, Arita, M, Lambeau, G, Droit, A, Boilard, E
JournalJCI Insight
Volume7
Issue2
Date Published2022 01 25
ISSN2379-3708
KeywordsAnimals, Animals, Genetically Modified, Arthritis, Bacterial Physiological Phenomena, Gastrointestinal Microbiome, Group II Phospholipases A2, Humans, Immune System Phenomena, Lipid Metabolism, Lipidomics, Mice, Models, Animal, Pathology, Molecular, Transgenes
Abstract

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.

DOI10.1172/jci.insight.152638
Alternate JournalJCI Insight
PubMed ID35076027
PubMed Central IDPMC8855825