Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae.
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.
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
Tom H M
TH
Ottenhoff
Frank A W
FA
Verreck
Elgin G R
EG
Lichtenauer-Kaligis
Marieke A
MA
Hoeve
Ozden
O
Sanal
Jaap T
JT
van Dissel
D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D053762:Interleukin-12 Subunit p40; D009164:Mycobacterium Infections / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D021122:Protein Subunits; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D012480:Salmonella Infections / Q000235:genetics* / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000096743:Interferon gamma Receptor
D016207:Cytokines; D004268:DNA-Binding Proteins; D007371:Interferon-gamma; D018664:Interleukin-12; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human