Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii.

Tiffney, Ellen A.; Coombes, Janine L.; Legembre, Patrick; Flynn, Robin J.

Abstract

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.

Citation

TIFFNEY, E.A., COOMBES, J.L., LEGEMBRE, P. and FLYNN, R.J. 2022. Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii. Microbes and infection [online], 24(5), article number 104952. Available from: https://doi.org/10.1016/j.micinf.2022.104952

• Journal Article Type: Article
• Acceptance Date: Feb 12, 2022
• Online Publication Date: Jul 1, 2022
• Publication Date: Aug 31, 2022
• Deposit Date: Dec 13, 2022
• Publicly Available Date: Jul 2, 2023
• Journal: Microbes and Infection
• Print ISSN: 1286-4579
• Electronic ISSN: 1769-714X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 5
• Article Number: 104952
• DOI: https://doi.org/10.1016/j.micinf.2022.104952
• Keywords: Toxoplasma gondii; Macrophages; CD95L; Cleaved CD95L; FasL; JAK/STAT; Arginase
• Public URL: https://rgu-repository.worktribe.com/output/1744706