Negative Cross-Talk between TLR2/4-Independent AMPKα1 and TLR2/4-Dependent JNK Regulates S. pneumoniae-Induced Mucosal Innate Immune Response.
Negative Cross-Talk between TLR2/4-Independent AMPKα1 and TLR2/4-Dependent JNK Regulates S. pneumoniae-Induced Mucosal Innate Immune Response.
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DOI：
10.4049/jimmunol.2100901
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发表时间：
2022-10-15
期刊：
影响因子：
--
通讯作者：
Li JD
中科院分区：
文献类型：
--
作者：
Matsuyama S;Komatsu K;Lee BC;Tasaki Y;Miyata M;Xu H;Shuto T;Kai H;Li JD
Streptococcus pneumoniae (S. pneumoniae) is major cause of otitis media (OM) and life-threatening pneumonia. Overproduction of mucin, the major component of mucus, plays a critical role in the pathogenesis of both OM and pneumonia. However, the molecular mechanisms underlying the tight regulation of mucin up-regulation in the mucosal epithelium by S. pneumoniae infection remains largely unknown. In this study, we show that S. pneumoniae pneumolysin (PLY) activates adenosine monophosphate-activated protein kinase α1 (AMPKα1), the master regulator of energy homeostasis, which is required for S. pneumoniae-induced mucin MUC5AC up-regulation in vitro and in vivo. Moreover, we found that PLY activates AMPKα1 via cholesterol dependent-membrane binding of PLY and subsequent activation of Ca2+-CaMKKβ and Cdc42-MLK3 signaling axis in a TLR2/4-independent manner. AMPKα1 positively regulates PLY-induced MUC5AC expression via negative cross-talk with TLR2/4-dependent activation of MAPK JNK, the negative regulator of MUC5AC expression. Moreover, pharmacological inhibition of AMPKα1 suppressed MUC5AC induction in S. pneumoniae-induced OM mouse model, thereby demonstrating its therapeutic potential in suppressing mucus overproduction in OM. Taken together, our data unveil a novel mechanism by which negative cross-talk between TLR2/4-independent activation of AMPKα1 and TLR2/4-dependent activation of JNK tightly regulates S. pneumoniae pneumolysin-induced host mucosal innate immune response.
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影响因子：
12.8
作者：
Jeon SM
通讯作者：
Jeon SM
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
DOI：
10.1073/pnas.0608213104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Iliev, Asparouh I.;Djannatian, Jasmin Roya;Wouters, Fred S.
通讯作者：
Wouters, Fred S.
影响因子：
4.9
作者：
Kuhajda, F. P.
通讯作者：
Kuhajda, F. P.
影响因子：
4.8
作者：
Ha, Un-Hwan;Lim, Jae Hyang;Li, Jian-Dong
通讯作者：
Li, Jian-Dong