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

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

  • JCI Insight. 2022 Jan 25;7(2):e152638. doi: 10.1172/jci.insight.152638.
Etienne Doré 1 2,  Charles Joly-Beauparlant 3,  Satoshi Morozumi 4 5,  Alban Mathieu 3,  Tania Lévesque 1 2,  Isabelle Allaeys 1 2,  Anne-Claire Duchez 1,  Nathalie Cloutier 1,  Mickaël Leclercq 3,  Antoine Bodein 3,  Christine Payré 6,  Cyril Martin 7,  Agnes Petit-Paitel 6,  Michael H Gelb 8,  Manu Rangachari 9,  Makoto Murakami 10,  Laetitia Davidovic 6,  Nicolas Flamand 2 7,  Makoto Arita 4 5 11,  Gérard Lambeau 6,  Arnaud Droit 3,  Eric Boilard 1 2
Affiliations

Affiliations

  • 1 CHU de Québec-Université Laval Research Center, Department of Microbiology, Infectiology and Immunology, Quebec City, Quebec, Canada.
  • 2 ARThrite Research Center, University Laval, Quebec City, Quebec, Canada.
  • 3 CHU de Québec-Université Laval Research Center, Endocrinology and Nephrology Axis, Quebec City, Quebec, Canada.
  • 4 Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • 5 Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
  • 6 Côte d'Azur University, The French National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, UMR7275, Valbonne Sophia Antipolis, France.
  • 7 The Research Center of the University Institute of Cardiology and Pneumology of Quebec, Quebec City, Quebec, Canada.
  • 8 Department of Chemistry, University of Washington, Seattle, Washington, USA.
  • 9 CHU de Québec-Université Laval Research Center, Neurosciences Axis, Quebec City, Quebec, Canada.
  • 10 Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • 11 Cellular and Molecular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama-City University, Yokohama, Japan.
PMID: 35076027 DOI: 10.1172/jci.insight.152638
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.

Keywords

Arthritis; Inflammation; Microbiology; Molecular pathology; Mouse models.

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