title: TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens.
abstract: IFN-γ is a major cytokine that is critical for host resistance to a broad range of intracellular pathogens. Production of IFN-γ by natural killer and T cells is initiated by the recognition of pathogens by Toll-like receptors (TLRs). In an experimental model of toxoplasmosis, we have identified the presence of a nonlymphoid source of IFN-γ that was particularly evident in the absence of TLR-mediated recognition of Toxoplasma gondii. Genetically altered mice lacking all lymphoid cells due to deficiencies in Recombination Activating Gene 2 and IL-2Rγc genes also produced IFN-γ in response to the protozoan parasite. Flow-cytometry and morphological examinations of non-NK/non-T IFN-γ(+) cells identified neutrophils as the cell type capable of producing IFN-γ. Selective elimination of neutrophils in TLR11(-/-) mice infected with the parasite resulted in acute susceptibility similar to that observed in IFN-γ-deficient mice. Similarly, Salmonella typhimurium infection of TLR-deficient mice induces the appearance of IFN-γ(+) neutrophils. Thus, neutrophils are a crucial source for IFN-γ that is required for TLR-independent host protection against intracellular pathogens.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA.
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Sturge
authors.forename: Alicia
authors.initials: A
authors.lastname: Benson
authors.forename: Megan
authors.initials: M
authors.lastname: Raetz
authors.forename: Cara L
authors.initials: CL
authors.lastname: Wilhelm
authors.forename: Julie
authors.initials: J
authors.lastname: Mirpuri
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
authors.forename: Felix
authors.initials: F
authors.lastname: Yarovinsky
mesh_terms: D000818:Animals; D006790:Host-Parasite Interactions / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000276:immunology / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology / Q000472:pathogenicity
chemical_list: C482903:Tlr11 protein, mouse; D051193:Toll-Like Receptors; D007371:Interferon-gamma
keywords: host defense; innate immunity