title: Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Kirk D C
authors.initials: KD
authors.lastname: Jensen
authors.forename: Yiding
authors.initials: Y
authors.lastname: Wang
authors.forename: Elia D Tait
authors.initials: ED
authors.lastname: Wojno
authors.forename: Anjali J
authors.initials: AJ
authors.lastname: Shastri
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hu
authors.forename: Lara
authors.initials: L
authors.lastname: Cornel
authors.forename: Erwan
authors.initials: E
authors.lastname: Boedec
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Ong
authors.forename: Yueh-hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
authors.forename: Jeroen P J
authors.initials: JP
authors.lastname: Saeij
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D014122:Toxoplasma / Q000145:classification / Q000235:genetics / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology
chemical_list: D015800:Protozoan Proteins