Unique Francisella Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid

• Published in: Journal of innate immunity Vol. 10; no. 4; pp. 291 - 305
• Main Authors: Ireland, Robin, Schwarz, Benjamin, Nardone, Glenn, Wehrly, Tara D., Broeckling, Corey D., Chiramel, Abhilash I., Best, Sonja M., Bosio, Catharine M.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018
• Subjects: Research Article; Dendritic cell; Bacteria; Phosphatidylethanolamine; Inflammation; Macrophage
• ISSN: 1662-811X; 1662-8128; 1662-8128
• DOI: 10.1159/000489504

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.