Title

Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections

UMMS Affiliation

Program in Molecular Medicine

Date

8-1-2007

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Immunology of Infectious Disease | Molecular Biology

Abstract

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-kappaB 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.

Rights and Permissions

Citation: Immunity. 2007 Aug;27(2):349-60. Link to article on publisher's site

Comments

Full author list omitted for brevity. For full list of authors see article.

Related Resources

Link to Article in PubMed

PubMed ID

17723219