The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses

Longfei Chen, David A. Christian, Joshua A. Kochanowsky, Anthony T. Phan, Joseph T. Clark, Shuai Wang, Corbett Berry, Jung Oh, Xiaoguang Chen, David S. Roos, Daniel P. Beiting, Anita A. Koshy, Christopher A. Hunter

Research output: Contribution to journalArticle

Abstract

The ability of Toxoplasma gondii to inject the rhoptry kinase ROP16 into host cells results in the activation of the transcription factors STAT3 and STAT6, but it is unclear how these events impact infection. Here, parasites that inject Cre-recombinase with rhoptry proteins were used to distinguish infected macrophages from those only injected with parasite proteins. Transcriptional profiling revealed that injection of rhoptry proteins alone was sufficient to induce an M2 phenotype that is dependent on STAT3 and STAT6, but only infected cells displayed reduced expression of genes associated with antimicrobial activity and protective immunity. In vivo, the absence of STAT3 or STAT6 improved parasite control, while the loss of ROP16 resulted in a marked reduction in parasite numbers and heightened parasite-specific T cell responses. Thus, ROP16 is a virulence factor that can act in cis and trans to promote M2 programs and which limits the magnitude of parasite-specific T cell responses.

Original languageEnglish (US)
JournalThe Journal of experimental medicine
Volume217
Issue number3
DOIs
Publication statusPublished - Mar 2 2020

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Chen, L., Christian, D. A., Kochanowsky, J. A., Phan, A. T., Clark, J. T., Wang, S., ... Hunter, C. A. (2020). The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses. The Journal of experimental medicine, 217(3). https://doi.org/10.1084/jem.20181757