Genetics of host response to Leishmania tropica in mice - different control of skin pathology, chemokine reaction, and invasion into spleen and liver.
BACKGROUND
Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models.


METHODS
We studied susceptibility to L. tropica, using BALB/c-c-STS/A (CcS/Dem) recombinant congenic (RC) strains, which differ greatly in susceptibility to L. major. Mice were infected with L. tropica and skin lesions, cytokine and chemokine levels in serum, and parasite numbers in organs were measured.


RESULTS
Females of BALB/c and several RC strains developed skin lesions. In some strains parasites visceralized and were detected in spleen and liver. Importantly, the strain distribution pattern of symptoms caused by L. tropica was different from that observed after L. major infection. Moreover, sex differently influenced infection with L. tropica and L. major. L. major-infected males exhibited either higher or similar skin pathology as females, whereas L. tropica-infected females were more susceptible than males. The majority of L. tropica-infected strains exhibited increased levels of chemokines CCL2, CCL3 and CCL5. CcS-16 females, which developed the largest lesions, exhibited a unique systemic chemokine reaction, characterized by additional transient early peaks of CCL3 and CCL5, which were not present in CcS-16 males nor in any other strain.


CONCLUSIONS
Comparison of L. tropica and L. major infections indicates that the strain patterns of response are species-specific, with different sex effects and largely different host susceptibility genes.
Laboratory of Molecular and Cellular Immunology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Tetyana
T
Kobets
Helena
H
Havelková
Igor
I
Grekov
Valeriya
V
Volkova
Jarmila
J
Vojtíšková
Martina
M
Slapničková
Iryna
I
Kurey
Yahya
Y
Sohrabi
Milena
M
Svobodová
Peter
P
Demant
Marie
M
Lipoldová
D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D007895:Leishmania tropica / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000469:parasitology*; D008099:Liver / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load; D012737:Sex Factors; D012867:Skin / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000469:parasitology
D016207:Cytokines