First Author | Morimoto N | Year | 2010 |
Journal | Biochem Biophys Res Commun | Volume | 401 |
Issue | 3 | Pages | 385-9 |
PubMed ID | 20854790 | Mgi Jnum | J:166166 |
Mgi Id | MGI:4839856 | Doi | 10.1016/j.bbrc.2010.09.062 |
Citation | Morimoto N, et al. (2010) Requirement of SIRPalpha for protective immunity against Leishmania major. Biochem Biophys Res Commun 401(3):385-9 |
abstractText | Signal regulatory protein alpha (SIRPalpha) is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on dendritic cells and macrophages. Wild-type (WT) C57BL/6 mice are known to be resistant to Leishmania major infection. We here found that C57BL/6 mice that express a mutant version of SIRPalpha lacking most of the cytoplasmic region manifested increased susceptibility to L. major infection, characterized by the marked infiltration of inflammatory cells in the infected lesions. The numbers of the parasites in footpads, draining lymph nodes and spleens were also markedly increased in the infected SIRPalpha mutant mice, compared with those for the infected WT mice. In addition, soluble leishmanial antigen-induced production of IFN-gamma by splenocytes of the infected SIRPalpha mutant mice was markedly reduced. By contrast, the ability of macrophages of SIRPalpha mutant mice to produce nitric oxide in response to IFN-gamma was almost equivalent to that of macrophages from WT mice. These results suggest that SIRPalpha is indispensable for protective immunity against L. major by the induction of Th1 response. |