| First Author | Xin L | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 12 | Pages | 7047-56 |
| PubMed ID | 20483775 | Mgi Jnum | J:161135 |
| Mgi Id | MGI:4457423 | Doi | 10.4049/jimmunol.0903273 |
| Citation | Xin L, et al. (2010) Type I IFN receptor regulates neutrophil functions and innate immunity to Leishmania parasites. J Immunol 184(12):7047-56 |
| abstractText | 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. |
