Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses. Journal Article


Authors: Chen, X; Alonzo, F
Article Title: Bacterial lipolysis of immune-activating ligands promotes evasion of innate defenses.
Abstract: Commensal and pathogenic bacteria hydrolyze host lipid substrates with secreted lipases and phospholipases for nutrient acquisition, colonization, and infection. Bacterial lipase activity on mammalian lipids and phospholipids can promote release of free fatty acids from lipid stores, detoxify antimicrobial lipids, and facilitate membrane dissolution. The gram-positive bacterium secretes at least two lipases, Sal1 and glycerol ester hydrolase (Geh), with specificities for short- and long-chain fatty acids, respectively, each with roles in the hydrolysis of environmental lipids. In a recent study from our group, we made the unexpected observation that Geh released by inhibits activation of innate immune cells. Herein, we investigated the possibility that lipases interface with the host immune system to blunt innate immune recognition of the microbe. We found that the Geh lipase, but not other lipases, prevents activation of innate cells in culture. Mutation of leads to enhancement of proinflammatory cytokine production during infection, increased innate immune activity, and improved clearance of the bacterium in infected tissue. These in vitro and in vivo effects on innate immunity were not due to direct functions of the lipase on mammalian cells, but rather a result of inactivation of lipoproteins, a major pathogen-associated molecular pattern (PAMP) of extracellular gram-positive bacteria, via ester hydrolysis. Altogether, these studies provide insight into an adaptive trait that masks microbial recognition by innate immune cells through targeted inactivation of a broadly conserved PAMP.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490; 0027-8424
Publisher: Unknown  
Date Published: 2019