Requirement of SIRPα for protective immunity against Leishmania major.
Signal regulatory protein α (SIRPα) 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 SIRPα 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 SIRPα mutant mice, compared with those for the infected WT mice. In addition, soluble leishmanial antigen-induced production of IFN-γ by splenocytes of the infected SIRPα mutant mice was markedly reduced. By contrast, the ability of macrophages of SIRPα mutant mice to produce nitric oxide in response to IFN-γ was almost equivalent to that of macrophages from WT mice. These results suggest that SIRPα is indispensable for protective immunity against L. major by the induction of Th1 response.
Morimoto
Naoko
N
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Murata
Yoji
Y
Motegi
Sei-ichiro
S
Suzue
Kazutomo
K
Saito
Yasuyuki
Y
Okazawa
Hideki
H
Ohnishi
Hiroshi
H
Kotani
Takenori
T
Kusakari
Shinya
S
Ishikawa
Osamu
O
Matozaki
Takashi
T
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D020022:Genetic Predisposition to Disease; D016898:Interferon-alpha / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000276:immunology
D000953:Antigens, Protozoan; D016898:Interferon-alpha; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D009569:Nitric Oxide