Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae

Tom H M Ottenhoff; Frank A W Verreck; Elgin G R Lichtenauer-Kaligis; Marieke A Hoeve; Ozden Sanal; Jaap T van Dissel

doi:10.1038/ng0902-97

Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae

Nat Genet. 2002 Sep;32(1):97-105. doi: 10.1038/ng0902-97.

Authors

Tom H M Ottenhoff¹, Frank A W Verreck, Elgin G R Lichtenauer-Kaligis, Marieke A Hoeve, Ozden Sanal, Jaap T van Dissel

Affiliation

¹ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. T.H.M.Ottenhoff@lumc.nl

PMID: 12205477
DOI: 10.1038/ng0902-97

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-gamma. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: interleukin-12p40, interleukin-12R beta 1, interferon-gamma R1, interferon-gamma R2 or STAT1. Ten syndromes have thus far been identified. Recent insights in genetically controlled host defense and susceptibility to mycobacterial disease are discussed.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cytokines / genetics*
Cytokines / immunology
DNA-Binding Proteins / genetics
DNA-Binding Proteins / immunology
Genetic Predisposition to Disease
Humans
Interferon gamma Receptor
Interferon-gamma / genetics
Interferon-gamma / immunology
Interleukin-12 / genetics
Interleukin-12 / immunology
Interleukin-12 Subunit p40
Mycobacterium Infections / genetics*
Mycobacterium Infections / immunology
Phenotype
Protein Subunits
Receptors, Interferon / genetics
Receptors, Interferon / immunology
Receptors, Interleukin / genetics
Receptors, Interleukin / immunology
Receptors, Interleukin-12
STAT1 Transcription Factor
Salmonella Infections / genetics*
Salmonella Infections / immunology
Trans-Activators / genetics
Trans-Activators / immunology
Tumor Necrosis Factor-alpha / metabolism

Substances

Cytokines
DNA-Binding Proteins
Interleukin-12 Subunit p40
Protein Subunits
Receptors, Interferon
Receptors, Interleukin
Receptors, Interleukin-12
STAT1 Transcription Factor
STAT1 protein, human
Trans-Activators
Tumor Necrosis Factor-alpha
Interleukin-12
Interferon-gamma