RGD Reference Report - Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages. - Rat Genome Database

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Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages.

Authors: Pathak, Sushil Kumar  Basu, Sanchita  Bhattacharyya, Asima  Pathak, Shresh  Kundu, Manikuntala  Basu, Joyoti 
Citation: Pathak SK, etal., J Biol Chem. 2005 Dec 30;280(52):42794-800. doi: 10.1074/jbc.M506471200. Epub 2005 Nov 1.
RGD ID: 36049804
Pubmed: (View Article at PubMed) PMID:16263713
DOI: Full-text: DOI:10.1074/jbc.M506471200

Mannose-capped lipoarabinomannans (Man-LAMs) are members of the repertoire of Mycobacterium tuberculosis modulins that the bacillus uses to subvert the host innate immune response. Interleukin-12 (IL-12) production is critical for mounting an effective immune response by the host against M. tuberculosis. We demonstrate that Man-LAM inhibits IL-12 p40 production mediated by subsequent challenge with lipopolysaccharide (LPS). Man-LAM inhibits LPS-induced IL-12 p40 expression in an IL-10-independent manner. It attenuates LPS-induced NF-kappaB-driven luciferase gene expression, suggesting that its effects are likely directly related to inhibition of NF-kappaB. This is probably because of dampening of the Toll-like receptor signaling. Man-LAM inhibits IL-1 receptor-associated kinase (IRAK)-TRAF6 interaction as well as IkappaB-alpha phosphorylation. It directly attenuates nuclear translocation and DNA binding of c-Rel and p50. Man-LAM exerts these effects by inducing the expression of Irak-M, a negative regulator of TLR signaling. Knockdown of Irak-M expression by RNA interference reinstates LPS-induced IL-12 production in Man-LAM-pretreated cells. The fact that Irak-M expression could be elicited by yeast mannan suggested that ligation of the mannose receptor by the mannooligosaccharide caps of LAM was the probable trigger for IRAK-M induction.

Annotation

Gene-Chemical Interaction Annotations    
lipoarabinomannan  (EXP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Irak3  (interleukin-1 receptor-associated kinase 3)

Genes (Mus musculus)
Irak3  (interleukin-1 receptor-associated kinase 3)

Genes (Homo sapiens)
IRAK3  (interleukin 1 receptor associated kinase 3)


Additional Information