Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice

Lucia E. Rosas, Tracy Keiser, Joseph Barbi, Anjali A. Satoskar, Alecia Septer, Jennifer Kaczmarek, Claudio M. Lezama-Davila, Abhay R. Satoskar
2005 International Immunology  
The experimental model of high-dose Leishmania mexicana infection is used frequently to study molecular mechanisms regulating T h 2 response since most inbred mice regardless of their genetic background display T h 2 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
more » ... ins 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 T h 2-associated cytokines and developed non-healing lesions full of parasites, whereas CBA/J mice preferentially produced T h 1-associated IFN-c but low levels of IL-4, and developed small self-resolving lesions. Both BALB/c and C57BL/6 mice produced comparable amounts of IFN-c following L. mexicana infection, but later produced less T h 2-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, CD41 T cells and CD81 T cells into their lesions. Finally, we analyzed the course of low-dose L. mexicana infection in signal transducers and activators of transcription (STAT) 6ÿ/ÿ and STAT61/1 BALB/c mice. We found that STAT6ÿ/ÿ mice mount a T h 1 response, produce high levels of IL-12 and IFN-c and develop smaller lesions containing fewer parasites as compared with STAT61/1 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.
doi:10.1093/intimm/dxh313 pmid:16141242 fatcat:gvebadd7vjeqvmvofilftaaspq