Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation

Kirk D C Jensen, Yiding Wang, Elia D Tait Wojno, Anjali J. Shastri, Kenneth Hu, Lara Cornel, Erwan Boedec, Yi Ching Ong, Yueh Hsiu Chien, Christopher A. Hunter, John C. Boothroyd, Jeroen Saeij

Research output: Contribution to journalArticle

120 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-κB, 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 (US)
Pages (from-to)472-483
Number of pages12
JournalCell Host and Microbe
Volume9
Issue number6
DOIs
StatePublished - Jun 16 2011
Externally publishedYes

Fingerprint

Toxoplasma
Macrophages
Inflammation
Parasites
Ileitis
Macrophage Activation
Infection
Virulence
Immunity
Phosphotransferases
Research
Genes
Proteins

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. / Jensen, Kirk D C; Wang, Yiding; Wojno, Elia D Tait; Shastri, Anjali J.; Hu, Kenneth; Cornel, Lara; Boedec, Erwan; Ong, Yi Ching; Chien, Yueh Hsiu; Hunter, Christopher A.; Boothroyd, John C.; Saeij, Jeroen.

In: Cell Host and Microbe, Vol. 9, No. 6, 16.06.2011, p. 472-483.

Research output: Contribution to journalArticle

Jensen, KDC, Wang, Y, Wojno, EDT, Shastri, AJ, Hu, K, Cornel, L, Boedec, E, Ong, YC, Chien, YH, Hunter, CA, Boothroyd, JC & Saeij, J 2011, 'Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation', Cell Host and Microbe, vol. 9, no. 6, pp. 472-483. https://doi.org/10.1016/j.chom.2011.04.015
Jensen, Kirk D C ; Wang, Yiding ; Wojno, Elia D Tait ; Shastri, Anjali J. ; Hu, Kenneth ; Cornel, Lara ; Boedec, Erwan ; Ong, Yi Ching ; Chien, Yueh Hsiu ; Hunter, Christopher A. ; Boothroyd, John C. ; Saeij, Jeroen. / Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation. In: Cell Host and Microbe. 2011 ; Vol. 9, No. 6. pp. 472-483.
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