Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection |
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Authors: | Iryna Kurey Tetyana Kobets Helena Havelková Martina Slapničková Lei Quan Kateřina Trtková Igor Grekov Milena Svobodová Alphons P Stassen Alan Hutson Peter Demant Marie Lipoldová |
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Institution: | 1. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20, Prague 4, Czech Republic 2. Roswell Park Cancer Institute, Buffalo, NY, 14263, USA 5. Laboratory of Molecular Pathology and Institute of Pathology, Faculty of Medicine, Palacky University, Hněvotínská 3, Olomouc, Czech Republic 3. Faculty of Science, Charles University, 128 44, Prague, Czech Republic 4. Department of Clinical Genomics, University of Maastricht, Maastricht, The Netherlands
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Abstract: | Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. 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 a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites’ elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c?×?CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNγ levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNγ), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype—Lmr21: skin lesions and IFNγ levels, Lmr22: IL-4 levels, Lmr23: IFNγ levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread. |
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