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

Carolyn R. Sturge, Alicia Benson, Megan Raetz, Cara L. Wilhelm, Julie Mirpuri, Ellen S. Vitetta, Felix Yarovinsky

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)10711-10716
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number26
DOIs
StatePublished - Jun 25 2013

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Toll-Like Receptors
Neutrophils
Parasites
Natural Killer T-Cells
Salmonella Infections
Toxoplasmosis
Toxoplasma
Salmonella typhimurium
Genetic Recombination
Genes
Interleukin-2
Flow Cytometry
Theoretical Models
Lymphocytes
Cytokines

Keywords

  • Host defense
  • Innate immunity

ASJC Scopus subject areas

  • General

Cite this

TLR-independent neutrophil-derived IFN-γ is important for host resistance to intracellular pathogens. / Sturge, Carolyn R.; Benson, Alicia; Raetz, Megan; Wilhelm, Cara L.; Mirpuri, Julie; Vitetta, Ellen S.; Yarovinsky, Felix.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 26, 25.06.2013, p. 10711-10716.

Research output: Contribution to journalArticle

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