JCI Insight (Jan 2022)

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

  • Etienne Doré,
  • Charles Joly-Beauparlant,
  • Satoshi Morozumi,
  • Alban Mathieu,
  • Tania Lévesque,
  • Isabelle Allaeys,
  • Anne-Claire Duchez,
  • Nathalie Cloutier,
  • Mickaël Leclercq,
  • Antoine Bodein,
  • Christine Payré,
  • Cyril Martin,
  • Agnes Petit-Paitel,
  • Michael H. Gelb,
  • Manu Rangachari,
  • Makoto Murakami,
  • Laetitia Davidovic,
  • Nicolas Flamand,
  • Makoto Arita,
  • Gérard Lambeau,
  • Arnaud Droit,
  • Eric Boilard

Journal volume & issue
Vol. 7, no. 2

Abstract

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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.

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