International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

WEDNESDAY 12 NOVEMBER
09:30 – 09:45 HRS

WOUND REPAIR AN IMPORTANT PATHWAY IN RESISTANCE TO L. MAJOR INFECTION

Foote S
The Walter and Eliza Hall Institute

Co-Authors: Handman E, Ellso C, Speed T, Smyth G, Sakthianandeswaren A, Curtis J, Kumar B
Institutions: The Walter and Eliza Hall Institute

We have mapped 3 QTLsin he mouse which modulate response to infection by L. major. These loci have been isolated onto isogenic backgrounds, both susceptible and resistant. These animals have a phenotype which is partway between that of the resistant and susceptible parents. A compound congenic animal has been bred with all three loci on both susceptible and resistant backgrounds. These animals can be fully resistant or susceptible, although the penetrance is not as complete as the parental lines.

Dogma has it that the T cell helper responses are important in determining outcome in this disease. We have measured the T cell responses in our congenic animals and found that there is no difference between the congenics and their backcross parental strain indicating that the Th response is not playing any role in these animals.

We have performed a microarray analysis on infected and unifected macrophages (the host cell) on compound congenic animals from both susceptible and resistant backgrounds. Among many genes differing between these animals were genes involved in wound healing. We therefore examined the wound healing response in our congenic mice and found a considerable difference. This difference was seen in both new wounds and in the response to the leishmania lesion itself. We conclude therefore that wound healing plays a major role in the host response to cutaneous leishmaniasis.


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