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

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

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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

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Leishmania
Innate Immunity
Parasites
Neutrophils
Neutrophil Infiltration
Monocytes
Parasitic Diseases
Leishmaniasis
Adoptive Transfer
Virus Diseases
Infection
Immunity
Macrophages
Apoptosis
Enzymes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites. / Xin, Lijun; Vargas-Inchaustegui, Diego A.; Raimer, Sharon; Kelly, Brent; Hu, Jiping; Zhu, Leiyi; Sun, Jiaren; Soong, Lynn.

In: Journal of Immunology, Vol. 184, No. 12, 15.06.2010, p. 7047-7056.

Research output: Contribution to journalArticle

Xin, Lijun ; Vargas-Inchaustegui, Diego A. ; Raimer, Sharon ; Kelly, Brent ; Hu, Jiping ; Zhu, Leiyi ; Sun, Jiaren ; Soong, Lynn. / Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites. In: Journal of Immunology. 2010 ; Vol. 184, No. 12. pp. 7047-7056.
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