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HLA-class II genes modify outcome of Toxoplasma gondii infection

Mack, D G and Johnson, J J and Roberts, F and Roberts, C W and Estes, R G and David, C and Grumet, F C and McLeod, R (1999) HLA-class II genes modify outcome of Toxoplasma gondii infection. International Journal for Parasitology, 29 (9). pp. 1351-1358. ISSN 0020-7519

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Abstract

Associations between Human Leukocyte Antigen (HLA) (i.e. human major histocompatibility complex [MHC]) genes and susceptibility to infections and inflammatory processes have been described, but causal relationships have not been proven. We characterized effects of HLA-DQ alleles on outcome of congenital toxoplasma infection and found that among Caucasians, the DQ3 gene frequency was significantly higher in infected infants with hydrocephalus (0.783) than infected infants without hydrocephalus (0.444) or published normal controls (0.487). We then developed a novel animal model to definitively determine the effect of these HLA DQ molecules on the severity of toxoplasmosis. Human MHC-Class II transgenes reduced parasite burden and necrosis in brains of mice infected with Toxoplasma gondii. Consistent with the observed association between DQ3 and hydrocephalus in human infants, in the murine model the DQ3(DQ8; DQB1*0302) gene protected less than DQ1 (DQ6; DQB1*0601). Our findings definitively prove a cause and effect relationship between human MHC genes and resistance to infection, provide novel means to characterise human immune responses that are protective or pathogenic in infections, and are important for vaccine development.

Item type: Article
ID code: 33631
Keywords: Animals, brain, continental population groups, female, gene frequency, genes, MHC class II, HLA-DQ antigens, homozygote, humans, hydrocephalus, infant, infectious disease transmission, vertical, magnetic resonance imaging, male, mice, mice, transgenic, toxoplasmosis, congenital, Pharmacy and materia medica, Infectious Diseases, Parasitology
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 28 Sep 2011 16:30
    Last modified: 05 Sep 2014 11:00
    URI: http://strathprints.strath.ac.uk/id/eprint/33631

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