International Immunology Advance Access published online on September 2, 2005
International Immunology, doi:10.1093/intimm/dxh313
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1 Department of Microbiology, Immunology and Medical Genetics, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
* To whom correspondence should be addressed. The experimental model of high-dose Leishmania mexicana infection is used frequently to study molecular mechanisms regulating Th2 response since most inbred mice regardless of their genetic background display Th2 cytokine-dependent susceptibility to L. mexicana unlike Leishmania major. Here, we analyzed the course of L. mexicana infection in BALB/c, C57BL/6 and CBA/J mouse strains using low-dose ear infection model that mimics natural transmission. Although all three strains were equally susceptible to high-dose back rump L. mexicana infection, they displayed marked differences in their ability to control parasite growth after low-dose ear infection. Leishmania mexicana-infected BALB/c mice produced high levels of Th2-associated cytokines and developed non-healing lesions full of parasites, whereas CBA/J mice preferentially produced Th1-associated IFN-
Received June 6, 2005
Accepted July 29, 2005
Article
Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice
2 Department of Pathology, Immunology and Medical Genetics, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
3 Department of Microbiology, Immunology and Medical Genetics, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA; Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
Abhay R. Satoskar, E-mail: satoskar.2{at}osu.edu
Abstract 
but low levels of IL-4, and developed small self-resolving lesions. Both BALB/c and C57BL/6 mice produced comparable amounts of IFN- following L. mexicana infection, but later produced less Th2-associated cytokines, and exhibited an ‘intermediate’ susceptibility phenotype characterized by lesion sizes that were significantly smaller than BALB/c mice but larger than CBA/J mice. Interestingly, all three strains also showed marked differences in trafficking of macrophages, CD4+ T cells and CD8+ T cells into their lesions. Finally, we analyzed the course of low-dose L. mexicana infection in signal transducers and activators of transcription (STAT) 6-/- and STAT6+/+ BALB/c mice. We found that STAT6-/- mice mount a Th1 response, produce high levels of IL-12 and IFN- and develop smaller lesions containing fewer parasites as compared with STAT6+/+ mice. Our findings demonstrate that genetic background plays a critical role in determining susceptibility of inbred mice to low-dose L. mexicana infection. Furthermore, together with our previous findings, they show that STAT6-mediated signaling is involved in mediating susceptibility to L. mexicana following both high-dose back rump and low-dose ear dermis infection.
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