Proc Natl Acad Sci U S A. 2013 Jun 10. [Epub ahead of print]
TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens
Sturge CR, Benson A, Raetz M, Wilhelm CL, Mirpuri J, Vitetta ES, Yarovinsky F.
Departments of Immunology and Microbiology, and Cancer Immunobiology Center, University of Texas Southwestern Medical School, Dallas, TX 75390.
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.
PMID: 23754402 [PubMed - as supplied by publisher]