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Unique Francisella Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid.


ABSTRACT: Virulent Francisella tularensis subsp. tularensis (Ftt) is a dynamic, intracellular, bacterial pathogen. Its ability to evade and rapidly suppress host inflammatory responses is considered a key element for its profound virulence. We previously established that Ftt lipids play a role in inhibiting inflammation, but we did not determine the lipid species mediating this process. Here, we show that a unique, abundant, phosphatidylethanolamine (PE), present in Francisella, contributes to driving the suppression of inflammatory responses in human and mouse cells. Acyl chain lengths of this PE, C24: 0 and C10: 0, were key to the suppressive capabilities of Francisella PE. Addition of synthetic PE 24: 0-10: 0 resulted in the accumulation of PE in host cells for up to 24 h of incubation, and recapitulated the inhibition of inflammatory responses observed with native Ftt PE. Importantly, this novel PE significantly inhibited inflammatory responses driven by a medically and globally important flavivirus, dengue fever virus. Thus, targeting these lipids and/or the pathways that they manipulate represents a new strategy to combat immunosuppression engendered by Ftt, but they also show promise as a novel therapeutic intervention for significant viral infections.

SUBMITTER: Ireland R 

PROVIDER: S-EPMC6757151 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Unique Francisella Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid.

Ireland Robin R   Schwarz Benjamin B   Nardone Glenn G   Wehrly Tara D TD   Broeckling Corey D CD   Chiramel Abhilash I AI   Best Sonja M SM   Bosio Catharine M CM  

Journal of innate immunity 20180703 4


Virulent Francisella tularensis subsp. tularensis (Ftt) is a dynamic, intracellular, bacterial pathogen. Its ability to evade and rapidly suppress host inflammatory responses is considered a key element for its profound virulence. We previously established that Ftt lipids play a role in inhibiting inflammation, but we did not determine the lipid species mediating this process. Here, we show that a unique, abundant, phosphatidylethanolamine (PE), present in Francisella, contributes to driving the  ...[more]

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