Influence of Lsh, H-2, and an H-11-linked gene on visceralization and metastasis associated with Leishmania mexicana infection in mice.
Visceral infection and metastatic lesion development following intravenous or subcutaneous inoculation of Leishmania mexicana amastigotes were examined in different B10 congenic mouse strains carrying alternative alleles at Lsh, H-2, or H-11. The results show that, despite a failure to observe any differences in rates of expansion of primary lesions in mice inoculated subcutaneously, each of these genes could be shown to exert some influence during visceralization and metastatic spread of L. mexicana infection. Of particular interest were (i) the continuous advantage observed throughout 160 to 200 days of infection in Lshr versus Lshs mice, (ii) the association between structural gene polymorphism at H-2 and profound visceral and metastatic spread of the parasite producing disease phenotypes akin to diffuse cutaneous leishmaniasis and post-kala-azar dermal leishmaniasis in humans, and (iii) similar effects observed in mice differing at H-11, the functional basis for which involves modified expression of major histocompatibility complex class II molecules. The results are discussed in relation to the human disease and the possibility that homologs for each of these genes regulate leishmanial infections in humans.
Roberts
M
M
Department of Medical Parasitology, London School of Hygiene & Tropical Medicine, United Kingdom.
Alexander
J
J
Blackwell
J M
JM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006183:H-2 Antigens / Q000502:physiology; D006649:Histocompatibility Antigens; D007113:Immunity, Innate; D007894:Leishmania mexicana / Q000254:growth & development* / Q000276:immunology; D007896:Leishmaniasis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D008099:Liver / Q000469:parasitology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000469:parasitology; D013997:Time Factors
D006183:H-2 Antigens; D006649:Histocompatibility Antigens