Caveolin-1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity.
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.
Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota 58203, USA.
Qiang
Q
Guo
Nan
N
Shen
Kefei
K
Yuan
Jiaxin
J
Li
Hong
H
Wu
Yong
Y
Zeng
John
J
Fox
Arvind K
AK
Bansal
Brij B
BB
Singh
Hongwei
H
Gao
Min
M
Wu
D000818:Animals; D051242:Caveolin 1 / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D007378:Interleukins / Q000032:analysis; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008168:Lung / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000209:etiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000502:physiology*
D051242:Caveolin 1; C486767:Il27 protein, mouse; D007378:Interleukins; D050799:STAT5 Transcription Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3