Tumor Suppressor CYLD Regulates Acute Lung Injury in Lethal Streptococcus pneumoniae Infections

Jae Hyang Lim, Brigid Stirling, Jonathan Derry, Tomoaki Koga, Hirofumi Jono, Chang Hoon Woo, Haodong Xu, Patricia Bourne, Un Hwan Ha, Hajime Ishinaga, Haidong Xu, Ali Andalibi, Xin Hua Feng, Hongguang Zhu, Yuxian Huang, Wenhong Zhang, Xinhua Weng, Chen Yan, Zhinan Yin, David E. BrilesRoger J. Davis, Richard A. Flavell, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Streptococcus pneumoniae (S. pneumoniae) causes high early mortality in pneumococcal pneumonia, which is characterized by acute lung injury (ALI). The molecular mechanisms underlying ALI and the high early mortality remain unknown. Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-κB transcription factor signaling, its role in regulating bacteria-induced lethality, however, is unknown. Here, we showed that CYLD deficiency protected mice from S. pneumoniae pneumolysin (PLY)-induced ALI and lethality. CYLD was highly induced by PLY, and it inhibited MKK3-p38 kinase-dependent expression of plasminogen activator inhibitor-1 (PAI-1) in lung, thereby potentiating ALI and mortality. Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia.

Original languageEnglish
Pages (from-to)349-360
Number of pages12
Issue number2
StatePublished - 24 Aug 2007




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