title: Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-γ-dependent elimination of Paneth cells.
abstract: Activation of Toll-like receptors (TLRs) by pathogens triggers cytokine production and T cell activation, immune defense mechanisms that are linked to immunopathology. Here we show that IFN-γ production by CD4(+) T(H)1 cells during mucosal responses to the protozoan parasite Toxoplasma gondii resulted in dysbiosis and the elimination of Paneth cells. Paneth cell death led to loss of antimicrobial peptides and occurred in conjunction with uncontrolled expansion of the Enterobacteriaceae family of Gram-negative bacteria. The expanded intestinal bacteria were required for the parasite-induced intestinal pathology. The investigation of cell type-specific factors regulating T(H)1 polarization during T. gondii infection identified the T cell-intrinsic TLR pathway as a major regulator of IFN-γ production in CD4(+) T cells responsible for Paneth cell death, dysbiosis and intestinal immunopathology.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Raetz
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Cara L
authors.initials: CL
authors.lastname: Wilhelm
authors.forename: Donna
authors.initials: D
authors.lastname: Kirkland
authors.forename: Alicia
authors.initials: A
authors.lastname: Benson
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Sturge
authors.forename: Julie
authors.initials: J
authors.lastname: Mirpuri
authors.forename: Shipra
authors.initials: S
authors.lastname: Vaishnava
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Defranco
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gilpin
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D016923:Cell Death; D004755:Enterobacteriaceae / Q000254:growth & development* / Q000276:immunology; D004756:Enterobacteriaceae Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions; D054884:Host-Pathogen Interactions; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D019879:Paneth Cells / Q000382:microbiology / Q000469:parasitology / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000382:microbiology / Q000469:parasitology / Q000473:pathology*; D014122:Toxoplasma / Q000254:growth & development* / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000150:complications / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D023084:alpha-Defensins / Q000172:deficiency
chemical_list: D011948:Receptors, Antigen, T-Cell; D023084:alpha-Defensins; D018664:Interleukin-12; D007371:Interferon-gamma