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Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10711-6. doi: 10.1073/pnas.1307868110. Epub 2013 Jun 10.

TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens.

Author information

1
Department of Immunology, University of Texas Southwestern Medical School, Dallas, TX 75390, USA.

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.

KEYWORDS:

host defense; innate immunity

PMID:
23754402
PMCID:
PMC3696766
DOI:
10.1073/pnas.1307868110
[Indexed for MEDLINE]
Free PMC Article
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