HLA-class II genes modify outcome of Toxoplasma gondii infection

Douglas G. MacK, Jennifer J. Johnson, Fiona Roberts, Craig W. Roberts, Randee G. Estes, Chella David, F. Carl Grumet, Rima McLeod

Research output: Contribution to journalArticle

91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1351-1358
Number of pages8
JournalInternational Journal for Parasitology
Volume29
Issue number9
DOIs
StatePublished - Sep 1 1999

Keywords

  • Congenital Toxoplasma infection
  • Encephalitis
  • HLA genes
  • Hydrocephalus
  • Major histocompatibility genes
  • Parasite burden
  • Toxoplasma gondii
  • Toxoplasmosis

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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  • Cite this

    MacK, D. G., Johnson, J. J., Roberts, F., Roberts, C. W., Estes, R. G., David, C., Carl Grumet, F., & McLeod, R. (1999). HLA-class II genes modify outcome of Toxoplasma gondii infection. International Journal for Parasitology, 29(9), 1351-1358. https://doi.org/10.1016/S0020-7519(99)00152-6