The separate and combined effects of MHC genotype, parasite clone, and host gender on the course of malaria in mice.
BACKGROUND
The link between host MHC (major histocompatibility complex) genotype and malaria is largely based on correlative data with little or no experimental control of potential confounding factors. We used an experimental mouse model to test for main effects of MHC-haplotypes, MHC heterozygosity, and MHC x parasite clone interactions. We experimentally infected MHC-congenic mice (F2 segregants, homo- and heterozygotes, males and females) with one of two clones of Plasmodium chabaudi and recorded disease progression.


RESULTS
We found that MHC haplotype and parasite clone each have a significant influence on the course of the disease, but there was no significant host genotype by parasite genotype interaction. We found no evidence for overdominance nor any other sort of heterozygote advantage or disadvantage.


CONCLUSIONS
When tested under experimental conditions, variation in the MHC can significantly influence the course of malaria. However, MHC heterozygote advantage through overdominance or dominance of resistance cannot be assumed in the case of single-strain infections. Future studies might focus on the interaction between MHC heterozygosity and multiple-clone infections.
Wedekind
Claus
C
Department of Ecology and Evolution, University of Lausanne, Biophore, 1015 Lausanne, Switzerland. claus.wedekind@unil.ch
Walker
Mirjam
M
Little
Tom J
TJ
D000818:Animals; D002999:Clone Cells; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008288:Malaria / Q000235:genetics* / Q000469:parasitology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D016788:Plasmodium chabaudi; D012737:Sex Factors
D006183:H-2 Antigens