TY - JOUR
T1 - Caveolin-1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity
AU - Guo, Qiang
AU - Shen, Nan
AU - Yuan, Kefei
AU - Li, Jiaxin
AU - Wu, Hong
AU - Zeng, Yong
AU - Fox, John
AU - Bansal, Arvind K.
AU - Singh, Brij B.
AU - Gao, Hongwei
AU - Wu, Min
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Alveolar macrophage phagocytosis
KW - Cell signaling pathway
KW - Gram-negative bacterial infection
KW - Innate immunity
KW - Proinflammatory cytokines
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U2 - 10.1002/eji.201142051
DO - 10.1002/eji.201142051
M3 - Article
C2 - 22678904
AN - SCOPUS:84862119973
SN - 0014-2980
VL - 42
SP - 1500
EP - 1511
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -