Abstract
Leishmaniasis, a disease caused by Leishmania ssp. is among the most neglected infectious diseases. In humans, L. tropica causes cutaneous form of leishmaniasis, but can damage internal organs too.
The reasons for this variability are not known, and its genetic basis was never investigated. Therefore, analysis of genes affecting host's responses to this infection can elucidate the characteristics of individual host-parasite interactions.
Recombinant congenic strain CcS-16 carries 12.5% genes from the mouse strain STS/A on genetic background of the strain BALB/c, and it is more susceptible than BALB/c. In F2 hybrids between BALB/c and CcS-16 we detected and mapped eight gene-loci, Ltr1-8 (Leishmania tropica response 1-8) that control various manifestations of disease: skin lesions, splenomegaly, hepatomegaly, parasite numbers in spleen, liver, and inguinal lymph nodes, and serum level of CCL3, CCL5, and CCL7 after L. tropica infection.
These loci are functionally heterogeneous - each influences a different set of responses to the pathogen. Five loci co-localize with the previously described loci that control susceptibility to L. major, three are species-specific.
Ltr2 co-localizes not only with Lmr14 (Leishmania major response 14), but also with Ir2 influencing susceptibility to L. donovani and might therefore carry a common gene controlling susceptibility to leishmaniasis.