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

Title
NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression
Authors
Yang C.-S.Shin D.-M.Kim K.-H.Lee Z.-W.Lee C.-H.Park S.G.Bae Y.S.Jo E.-K.
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2009
Journal Title
Journal of Immunology
ISSN
0022-1767JCR Link
Citation
vol. 182, no. 6, pp. 3696 - 3705
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. Copyright © 2009 by The American Association of Immunologists, Inc.
DOI
10.4049/jimmunol.0802217
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자연과학대학 > 생명과학전공 > Journal papers
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