Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection.
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 x 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 IFNgamma levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNgamma), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype-Lmr21: skin lesions and IFNgamma levels, Lmr22: IL-4 levels, Lmr23: IFNgamma levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread.
Kurey
Iryna
I
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
Kobets
Tetyana
T
Havelková
Helena
H
Slapnicková
Martina
M
Quan
Lei
L
Trtková
Katerina
K
Grekov
Igor
I
Svobodová
Milena
M
Stassen
Alphons P
AP
Hutson
Alan
A
Demant
Peter
P
Lipoldová
Marie
M
D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008198:Lymph Nodes / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012727:Sex Characteristics; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000469:parasitology
D007371:Interferon-gamma
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