Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites

Lijun Xin, Diego A. Vargas-Inchaustegui, Sharon S. Raimer, Brent C. Kelly, Jiping Hu, Leiyi Zhu, Jiaren Sun, Lynn Soong

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Type I IFNs exert diverse effector and regulatory functions in host immunity to viral and nonviral infections; however, the role of endogenous type I IFNs in leishmaniasis is unclear. We found that type I IFNR-deficient (IFNAR-/-) mice developed attenuated lesions and reduced Ag-specific immune responses following infection with Leishmania amazonensis parasites. The marked reduction in tissue parasites, even at 3 d in IFNAR-/- mice, seemed to be indicative of an enhanced innate immunity. Further mechanistic analyses indicated distinct roles for neutrophils in parasite clearance; IFNAR-/- mice displayed a rapid and sustained infiltration of neutrophils, but a limited recruitment of CD11b+Ly-6C+ inflammatory monocytes, into inflamed tissues; interactions between IFNAR -/-, but not wild-type (WT) or STAT1-/-, neutrophils and macrophages greatly enhanced parasite killing in vitro; and infected IFNAR -/- neutrophils efficiently released granular enzymes and had elevated rates of cell apoptosis. Furthermore, although coinjection of parasites with WT neutrophils or adoptive transfer of WT neutrophils into IFNAR -/- recipients significantly enhanced infection, the coinjection of parasites with IFNAR-/- neutrophils greatly reduced parasite survival in WT recipients. Our findings reveal an important role for type I IFNs in regulating neutrophil/monocyte recruitment, neutrophil turnover, and Leishmania infection and provide new insight into innate immunity to protozoan parasites.

Original languageEnglish (US)
Pages (from-to)7047-7056
Number of pages10
JournalJournal of Immunology
Volume184
Issue number12
DOIs
StatePublished - Jun 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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