Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation

K.D.C. Jensen, Y. Wang, E.D. Tait Wonjo, A.J. Shastri, K. Hu, L. Cornel, E. Boedec, Y.C. Ong, Y.H. Chien, C.A. Hunter, J.C. Boothroyd, J.P.J. Saeij

Research output: Contribution to journalArticleAcademicpeer-review

139 Citations (Scopus)

Abstract

European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-¿B, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection
Original languageEnglish
Pages (from-to)472-483
JournalCell Host & Microbe
Volume9
Issue number6
DOIs
Publication statusPublished - 2011

Keywords

  • alternative activation
  • gene-expression
  • dendritic cells
  • interferon-gamma
  • gondii infection
  • virulence
  • population
  • arginase
  • phosphorylation
  • resistance

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