Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii.

Autor: Tiffney EA; Dept. Infection Biology, Institute of Infection and Global Health, University of Liverpool, L3 5RF, UK., Coombes JL; Dept. Infection Biology, Institute of Infection and Global Health, University of Liverpool, L3 5RF, UK., Legembre P; Centre Eugène Marquis, Université Rennes-1, INSERM U1242, Rennes, France., Flynn RJ; Dept. Infection Biology, Institute of Infection and Global Health, University of Liverpool, L3 5RF, UK; Graduate Studies Office, Department of Research, Innovation and Graduate Studies, Waterford Institute of Technology, X91 K0EK, Ireland. Electronic address: robin.flynn@wit.ie.
Jazyk: angličtina
Zdroj: Microbes and infection [Microbes Infect] 2022 Jul-Aug; Vol. 24 (5), pp. 104952. Date of Electronic Publication: 2022 Mar 01.
DOI: 10.1016/j.micinf.2022.104952
Abstrakt: Toxoplasma gondii infects approximately 1-2 billion people, and manipulation of the macrophage response is critical to host and parasite survival. A cleaved (cl)-CD95L form can promote cellular migration and we have previously shown that cl-CD95L aggravates inflammation and pathology in systemic lupus erythematosus (SLE). Findings have shown that CD95L is upregulated during human infection, therefore we examined the effect of cl-CD95L on the macrophage response to T. gondii. . We find that cl-CD95L promotes parasite replication in macrophages, associated with increased arginase-1 levels, mediated by signal transducer and activator of transcription (STAT)6. Inhibition of both arginase-1 and STAT6 reversed the effects of cl-CD95L. Phospho-kinase array showed that cl-CD95L alters Janus Kinases (JAK)/STAT, mammalian target of rapamycin (mTOR), and Src kinase signals. By triggering changes in JAK/STAT cl-CD95L may limit anti-parasite effectors.
Competing Interests: Declaration of competing interest RJF and PL are applicants on a patent surrounding the use of CD95 therapeutics.
(Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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