Supplementary Material for: Unique <b><i>Francisella</i></b> Phosphatidylethanolamine Acts as a Potent Anti-Inflammatory Lipid

Virulent <i>Francisella tularensis</i> subsp. <i>tularensis</i> (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 <i>Francisella</i>, 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 <i>Francisella</i> 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.