Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites.
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.
Xin
Lijun
L
Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Vargas-Inchaustegui
Diego A
DA
Raimer
Sharon S
SS
Kelly
Brent C
BC
Hu
Jiping
J
Zhu
Leiyi
L
Sun
Jiaren
J
Soong
Lynn
L
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007113:Immunity, Innate; D007891:Leishmania / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053633:Receptor, Interferon alpha-beta