Caveolin-1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity

Qiang Guo, Nan Shen, Kefei Yuan, Jiaxin Li, Hong Wu, Yong Zeng, John Fox, Arvind K. Bansal, Brij B. Singh, Hongwei Gao, Min Wu

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Caveolin-1 (Cav1) is a structural protein of caveolae. Although Cav1 is associated with certain bacterial infections, it is unknown whether Cav1 is involved in host immunity against Klebsiella pneumoniae, the third most commonly isolated microorganism from bacterial sepsis patients. Here, we showed that cav1 knockout mice succumbed to K. pneumoniae infection with markedly decreased survival rates, increased bacterial burdens, intensified tissue injury, hyperactive proinflammatory cytokines, and systemic bacterial dissemination as compared with WT mice. Knocking down Cav1 by a dominant negative approach in lung epithelial MLE-12 cells resulted in similar outcomes (decreased bacterial clearance and increased proinflammatory cytokine production). Furthermore, we revealed that STAT5 influences the GSK3β-β-catenin-Akt pathway, which contributes to the intensive inflammatory response and rapid infection dissemination seen in Cav1 deficiency. Collectively, our findings indicate that Cav1 may offer resistance to K. pneumoniae infection, by affecting both systemic and local production of proinflammatory cytokines via the actions of STAT5 and the GSK3β-β-catenin-Akt pathway.

Original languageEnglish (US)
Pages (from-to)1500-1511
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Alveolar macrophage phagocytosis
  • Cell signaling pathway
  • Gram-negative bacterial infection
  • Innate immunity
  • Proinflammatory cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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