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

ABSTRACT: IFN-? is a major cytokine that is critical for host resistance to a broad range of intracellular pathogens. Production of IFN-? 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-? 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-2R?c genes also produced IFN-? in response to the protozoan parasite. Flow-cytometry and morphological examinations of non-NK/non-T IFN-?(+) cells identified neutrophils as the cell type capable of producing IFN-?. Selective elimination of neutrophils in TLR11(-/-) mice infected with the parasite resulted in acute susceptibility similar to that observed in IFN-?-deficient mice. Similarly, Salmonella typhimurium infection of TLR-deficient mice induces the appearance of IFN-?(+) neutrophils. Thus, neutrophils are a crucial source for IFN-? that is required for TLR-independent host protection against intracellular pathogens.

SUBMITTER: Sturge CR 

PROVIDER: S-EPMC3696766 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature