Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia

Department of Microbiology and Immunology Department of Medicine, Division of Cardiology Department of Pathology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Aging cell (Impact Factor: 5.94). 05/2011; 10(5):798-806. DOI: 10.1111/j.1474-9726.2011.00720.x
Source: PubMed

ABSTRACT Cellular senescence is an age-associated phenomenon that promotes tumor invasiveness owing to the secretion of proinflammatory cytokines, proteases, and growth factors. Herein we demonstrate that cellular senescence also potentially increases susceptibility to bacterial pneumonia caused by Streptococcus pneumoniae (the pneumococcus), the leading cause of infectious death in the elderly. Aged mice had increased lung inflammation as determined by cytokine analysis and histopathology of lung sections. Immunoblotting for p16, pRb, and mH2A showed that elderly humans and aged mice had increased levels of these senescence markers in their lungs vs. young controls. Keratin 10 (K10), laminin receptor (LR), and platelet-activating factor receptor (PAFr), host proteins known to be co-opted for bacterial adhesion, were also increased. Aged mice were found to be highly susceptible to pneumococcal challenge in a PsrP, the pneumococcal adhesin that binds K10, dependent manner. In vitro senescent A549 lung epithelial cells had elevated K10 and LR protein levels and were up to 5-fold more permissive for bacterial adhesion. Additionally, exposure of normal cells to conditioned media from senescent cells doubled PAFr levels and pneumococcal adherence. Genotoxic stress induced by bleomycin and oxidative stress enhanced susceptibility of young mice to pneumonia and was positively correlated with enhanced p16, inflammation, and LR levels. These findings suggest that cellular senescence facilitates bacterial adhesion to cells in the lungs and provides an additional molecular mechanism for the increased incidence of community-acquired pneumonia in the elderly. This study is the first to suggest a second negative consequence for the senescence-associated secretory phenotype.

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Available from: Claude Le Saux, Jul 08, 2015
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    • "Thus, the cellular senescence is an important cellular status that allows the damaged cells to adapt to stress or undergo programmed cell death in the pathogenesis of COPD/emphysema. The cellular senescence also facilitates bacterial adhesion to the lung cells under the persistent SIPS leading to exacerbations of the disease (Shivshankar et al., 2011; Zhou et al., 2011). "
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    • "Importantly, exposure of A549 cells to conditioned media from senescent lung cells was able to increase the expression of PAFr and increase their permissiveness to pneumococcal adhesion [47]. Thus, we propose a model by which the accumulation of senescent lung cells due to aging or exposure to genotoxic agents such as cigarette smoke could enhance LR, PAFr and K10 in the lungs thereby promoting bacterial attachment and susceptibility to pneumococcal pneumonia (Figure 1). "
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