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Title 

NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression

Authors 

C S YangD M ShinK H KimZ W LeeChul Ho LeeSung Goo ParkY S BaeE K Jo

Publisher 

American Association of Immunologists

Issue Date 

2009

Citation 

Journal of Immunology, vol. 182, no. 6, pp. 3696-3705

Keywords 

reduced nicotinamide adenine dinucleotide phosphate oxidaseTlr2 protein, mousetoll like receptor 2innate immunitymycobacterium tuberculosisimmunity, innateNADPH

Abstract 

Gp91(phox)/NADPH oxidase (NOX) 2 is the main catalytic component of NOX, which mediates the phagocytic killing of ingested pathogens via the production of reactive oxygen species (ROS). However, Mycobacterium tuberculosis (Mtb) is relatively resistant to the microbicidal effects of ROS. Thus, the exact roles of NOX2 in the innate immune control against Mtb infection are not fully resolved. In this study, we show that NOX2 is essential for TLR2-dependent inflammatory responses and 1,25-dihydroxyvitamin D(3) (1,25D(3))-mediated antimicrobial activity against Mtb via cathelicidin expression. NOX2-null macrophages prominently abrogated Mtb-induced ROS production and inflammatory signaling activation in a TLR2-dependent manner. Mtb triggered a physical association between NOX2 and TLR2. In addition, the knockdown of NOX2 inhibited 1,25D(3)-triggered antimicrobial activity against viable Mtb through the modulation of cathelicidin expression in human macrophages. Treatment of NOX2 knocked down cells with cathelicidin restored the 1,25D(3)-induced antimicrobial effect, suggesting that the NOX2-dependent induction of cathelicidin in macrophages is part of a defensive strategy against Mtb. Furthermore, cathelicidin expression was required for the Mtb-induced release of ROS and the production of proinflammatory cytokines/chemokines, indicating a positive circuit of inflammation in response to Mtb. Our data collectively demonstrate a novel regulatory mechanism for TLR2-dependent innate responses to Mtb involving crosstalk between NOX2 and TLR2 and the expression of cathelicidin.

ISSN 

0022-1767

Link 

http://dx.doi.org/10.4049/jimmunol.0802217

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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