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In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 27, 2010
Requirement of SIRPα for protective immunity against Leishmania major
Naoko Morimoto1, Yoji Murata, Sei-ichiro Motegi
1Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Abstract:
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.
Insights
Signal regulatory protein α (SIRPα) is crucial for immunity against Leishmania major infection. Mutant mice lacking SIRPα cytoplasmic regions showed increased susceptibility and reduced protective Th1 responses.
Area of Science:
- Immunology
- Infectious Diseases
- Cell Biology
Background:
- Signal regulatory protein α (SIRPα) is a transmembrane protein on immune cells like macrophages and dendritic cells.
- Wild-type C57BL/6 mice are naturally resistant to Leishmania major infection.
- SIRPα interacts with SHP-1 and SHP-2 phosphatases via its cytoplasmic domain.
Purpose of the Study:
- To investigate the role of SIRPα's cytoplasmic region in Leishmania major infection resistance.
- To determine if SIRPα is essential for protective immunity against this parasite.
Main Methods:
- Comparison of Leishmania major infection susceptibility between wild-type and SIRPα mutant C57BL/6 mice.
- Assessment of inflammatory cell infiltration, parasite burden in tissues, and cytokine production (IFN-γ).
- Evaluation of macrophage nitric oxide production in response to IFN-γ.
Main Results:
- SIRPα mutant mice exhibited increased susceptibility to L. major infection.
- Mutant mice showed marked inflammatory cell infiltration and higher parasite loads.
- Reduced production of IFN-γ by splenocytes from infected SIRPα mutant mice was observed.
- Macrophage nitric oxide production was comparable between WT and mutant mice.
Conclusions:
- SIRPα, particularly its cytoplasmic region, is indispensable for protective immunity against Leishmania major.
- SIRPα plays a critical role in inducing the Th1 immune response necessary for controlling infection.
- The findings highlight SIRPα as a key regulator in host defense against parasitic infections.
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