Identification of a unique lipid from Francisella tularensis as an effective therapeutic for viral mediated inflammation

Autor: Catharine M Bosio, Glenn Nardone, Corey Broeckling, Abilash Chiramel, Sonja Best, Robin Ireland
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:76.24-76.24
ISSN: 1550-6606
0022-1767
Popis: Francisella tularensis (FT) is a highly pathogenic bacterium which can cause acute, lethal disease following exposure to fewer than 20 bacteria. FT is a successful pathogen due to its ability to potently and rapidly suppress inflammatory responses in host cells. We previously established that crude lipid preparations from virulent FT dampen inflammation in vitro and in vivo, but did not characterize the active specie(s). Utilizing a variety of biochemical techniques, we identified one of the active lipids found in FT as a unique phosphatidylethanolamine (PE) consisting of tetracosanoyl and decanoyl acyl chains (PE2410). Similar to crude lipid, enriched PE2410 restricted production of cytokines in human and mouse cells stimulated with well-defined microbial ligands. PE2410 was also effective at dampening inflammation provoked by infection with West Nile Virus. Activity of PE2410 was dependent on presence of the host phosphatase SHP-1. Importantly, a synthetic version of the PE2410 mimicked the ability of natural PE2410 to inhibit inflammation triggered by a variety of sources. Together our data support use of PE2410 as a novel therapeutic for pathogenic inflammation triggered by viral, or other, infection.
Databáze: OpenAIRE