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Review
. 2014 May;34(5):307-17.
doi: 10.1089/jir.2013.0050. Epub 2013 Dec 20.

Innate defects of the IL-12/IFN-γ axis in susceptibility to infections by mycobacteria and salmonella

Noé Ramirez-Alejo  1 , Leopoldo Santos-Argumedo
Affiliations
Review

Innate defects of the IL-12/IFN-γ axis in susceptibility to infections by mycobacteria and salmonella

Noé Ramirez-Alejo et al. J Interferon Cytokine Res. 2014 May.

Abstract

Since 1996, several studies characterizing the association between primary immunodeficiencies and susceptibility to infections with environmental and non-pathogenic mycobacteria such as the Bacillus Calmette-Guérin (Mycobacterium bovis Bacillus of Calmette Guérin strain) as well as disseminated infections by Salmonella spp. have been conducted. These conditions, grouped in the so-called Mendelian susceptibility to mycobacterial diseases, include a primary immunodeficiency caused by mutations in 7 autosomal genes (IFNGR1, IFNGR2, IL12B, IL12BR1, STAT1, ISG15, and IRF8) and an X-linked gene (NEMO). This syndrome presents a high degree of allelic heterogeneity and variable penetrance. This review focuses on the analysis of the first reported cases of these diseases, as well as on the molecular findings involved in each of them.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Immune response against mycobacteria and salmonella. T lymphocytes co-operates through interferon (IFN)-γ secretion, which activates the anti-microbial mechanisms in infected macrophages.
<b>FIG. 2.</b>
FIG. 2.
IL-17 participation in mycobacterial infection. Mycobacterial infection activates IL-23 secretion by infected macrophages. This cytokine regulates T-lymphocyte differentiation to TH17 population, which co-operates to control infection through IL-17 secretion.
<b>FIG. 3.</b>
FIG. 3.
Defective response to IFN-γ. Defects in IFN-γR1, IFN-γR2, and signal transducer and activator of transcription 1 (STAT1) result in unresponsiveness to IFN-γ and an inability to activate the anti-microbial mechanisms in macrophages.
<b>FIG. 4.</b>
FIG. 4.
Defective response to IL-12. Defects in IL-12p40 and IL-12Rβ1 impair IFN-γ production by T lymphocytes.
See this image and copyright information in PMC

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