Systematic assessment of the role of host genes in clinico-pathological and immunological manifestations of Leishmania major-induced disease in mice was performed using 20 recombinant congenic (RC) strains. As the RC strains are homozygous and each carries a different, random set of 12.5% genes from the resistant strain, STS/A, and 87.5% genes from the susceptible strain, BALB/cHeA, they allowed us to study the pathological and immunological characteristics of infected hosts in 20 fixed different random combinations of BALB/c and STS genes. The 20 RC strains differ widely in expression of different symptoms of disease and in immunological characteristics. Disease or healing in different strains occurred in association with different components of immune response -- with the exception of a frequently occurring correlation between the disease and IgE levels. Moreover, some parameters of the immune response were highly correlated in some strains but not at all in others. This shows that several patterns of the immune response may be associated with the same clinical outcome, depending on the host genotype. Our data also suggest that despite the complexity of regulation, when a sufficient number of controlling loci is known, the prediction of a phenotype is possible. Combining functional and clinical information with multilocus genotyping may improve our ability to predict the progression of the disease and to optimize the treatment.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Fleming nám 2 16637 Prague Czech Republic

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Effects of Leishmania major infection on the gut microbiome of resistant and susceptible mice

Functionally distinct regions of the locus Leishmania major response 15 control IgE or IFNγ level in addition to skin lesions

Genetic Influence on Frequencies of Myeloid-Derived Cell Subpopulations in Mouse

Novel Loci Controlling Parasite Load in Organs of Mice Infected With Leishmania major, Their Interactions and Sex Influence

Genetic Regulation of Guanylate-Binding Proteins 2b and 5 during Leishmaniasis in Mice

Gene-specific sex effects on eosinophil infiltration in leishmaniasis

Mapping the genes for susceptibility and response to Leishmania tropica in mouse

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Genetics of host response to Leishmania tropica in mice - different control of skin pathology, chemokine reaction, and invasion into spleen and liver

Genetic control of resistance to Trypanosoma brucei brucei infection in mice

Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection

Different genetic control of cutaneous and visceral disease after Leishmania major infection in mice