Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number104952
JournalMicrobes and Infection
Volume24
Issue number5
DOIs
Publication statusPublished - 01 Jul 2022

Keywords

  • Arginase
  • CD95L
  • Cleaved CD95L
  • JAK/STAT
  • Macrophage
  • Toxoplasma gondii

Fingerprint

Dive into the research topics of 'Cleaved CD95L perturbs in vitro macrophages responses to Toxoplasma gondii'. Together they form a unique fingerprint.

Cite this