Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection
Abstract
Leishmania major infection in mice is an important model of host-pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens and chronic disease with skin lesions, splenomegaly, hepatomegaly, increased serum IgE levels and cytokine imbalance.
Linkage analysis integrated with study of multiple manifestations of infection in (BALB/c x CcS-11) F2 hybrids mapped 5 loci, 2 of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (+ skin lesions, splenomegaly, serum IgE, IL-4, and IFNg levels) and Lmr20 determines parasite numbers in draining lymph nodes (+ serum IgE and IFNg levels) but no skin or visceral pathology.
Three additional loci do not affect parasite numbers but significantly influence disease phenotype - Lmr21: skin lesions, IFNg levels, Lmr22: IL-4 levels, Lmr23: IFNg levels, indicating that L. major-caused disease development includes critical regulations additional to control of parasite spread.