Abstract
Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guérin) or Salmonella species have been shown to be unable to produce or respond to interferon-γ. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: interleukin-12p40, interleukin-12Rβ1, interferon-γR1, interferon-γR2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.
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Acknowledgements
This work was supported by the Netherlands Leprosy Foundation, the Commission of the European Communities, Netherlands Organization for Scientific Research (NWO/ZON-MW) and the Royal Netherlands Academy of Arts and Sciences. We thank R.R.P. de Vries and C.J.M. Melief for critically reading the manuscript.
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Ottenhoff, T., Verreck, F., Lichtenauer-Kaligis, E. et al. Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae. Nat Genet 32, 97–105 (2002). https://doi.org/10.1038/ng0902-97
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DOI: https://doi.org/10.1038/ng0902-97
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