The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses
Christian, David A.
Kochanowsky, Joshua A.
Phan, Anthony T.
Clark, Joseph T.
Roos, David S.
Beiting, Daniel P.
Koshy, Anita A.
Hunter, Christopher A.
AffiliationUniv Arizona, BIO5 Inst, Dept Neurol
Univ Arizona, BIO5 Inst, Dept Immunobiol
MetadataShow full item record
PublisherROCKEFELLER UNIV PRESS
CitationLongfei 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; The Toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses. J Exp Med 2 March 2020; 217 (3): e20181757. doi: https://doi.org/10.1084/jem.20181757
JournalJOURNAL OF EXPERIMENTAL MEDICINE
Rights© 2020 Chen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractThe 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.
VersionFinal published version