Genetic dissection of host resistance to Mycobacterium tuberculosis: the sst1 locus and the Ipr1 gene.

Current Topics in Microbiology and Immunology
Igor Kramnik

Abstract

Genetic variation of the host significantly contributes to dramatic differences in the outcomes of natural infection with virulent Mycobacterium tuberculosis (MTB) in humans, as well as in experimental animal models. Host resistance to tuberculosis is a complex multifactorial genetic trait in which many genetic polymorphisms contribute to the phenotype, while their individual contributions are influenced by gene-gene and gene-environment interactions. The most epidemiologically significant form of tuberculosis infection in humans is pulmonary tuberculosis. Factors that predispose immunocompetent individuals to this outcome, however, are largely unknown. Using an experimental mouse model of infection with virulent MTB for the genetic analysis of host resistance to this pathogen, we have identified several tuberculosis susceptibility loci in otherwise immunocompetent mice. The sst1 locus has been mapped to mouse chromosome 1 and shown to be especially important for control of pulmonary tuberculosis. Rampant progression of tuberculosis infection in the lungs of the sst1-susceptible mouse was associated with the development of necrotic lung lesions, which was prevented by the sst1-resistant allele. Using a positional cloning approa...Continue Reading

Citations

Jan 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Susanna CommandeurTom H M Ottenhoff
Feb 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohammed M NoohMalak Kotb
Jul 14, 2012·Immunotherapy·T Mark Doherty
Apr 30, 2009·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Jes Dietrich, T Mark Doherty
Jan 22, 2011·Clinical & Developmental Immunology·Markos AbebeT Mark Doherty

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