Abstract
Streptococcus pneumonia, (Spn, the pneumococcus), is the leading cause of community-acquired pneumonia (CAP) and is responsible for 15–40% deaths in the elderly worldwide. A primed inflammatory status is a significant risk factor for the increased severity of infectious diseases among the elderly (≥65 years of age). Studies have shown that expression of host receptors that the pneumococci bind to invade the tissues are increased thereby increasing the susceptibility to pneumococcal challenge in aged mice. Cellular senescence, an age-related phenomenon that leads to cell cycle arrest may also contribute to increased inflammation in aged mice. Evidence of cellular senescence in aged lungs of humans and mice adds credits to the concept of inflammaging and enhanced bacterial ligands expression during aging. Furthermore, cell senescence has been shown to occur in age-associated lung pathologies such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) that may predispose the elderly to pathogenic assaults, including S. pneumoniae. This review highlights the aspects of: chronic inflammation in the aged population; contribution of cellular senescence to age-associated inflammation and their impact on host receptor expression; and, increased susceptibility of fibrosis and emphysematous lesions-bearing lungs to microbial infections.
Highlights
Aging is a multifactorial process that encompasses progressive decline in multiple organ failure, induced by chronic low-grade inflammation and stress-mediated imbalances
This review presents a comprehensive account of oppressive aging factors such as chronic inflammation, cell senescence and senescenceassociated secretory phenotype (SASP) in the aged lungs, and their role in age-associated lung pathologies such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), that are known to increase vulnerability of the aged patients to pneumococcal disease
We have demonstrated that chronic inflammation in aged mouse lungs stimulates NF-κB-regulated gene expression including the pneumococcus-binding proteins, polymeric immunoglobulin receptor, and platelet-activating factor receptor (PAFr)
Summary
Aging is a multifactorial process that encompasses progressive decline in multiple organ failure, induced by chronic low-grade inflammation and stress-mediated imbalances. We have recently demonstrated a second negative consequence of SASP as a modulator of NFκB-activated pneumococcal binding protein, platelet activating factor receptor (PAFr), due to the increased levels of IL-6 and IL-8 production in bleomycin-induced senescent type-II pneumocyte cultures [19]. We have demonstrated that chronic inflammation in aged mouse lungs stimulates NF-κB-regulated gene expression including the pneumococcus-binding proteins, polymeric immunoglobulin receptor (pIgR), and platelet-activating factor receptor (PAFr). Mitogenactivated protein kinase (MAPK) signaling, especially p38MAPK, is activated independent of DNA damage response in senescent cells, and it is associated with chronic stress-induced inflammation during aging [35]. Activation of these multiple signaling pathways increases NF-κB-regulated transcription of genes including production of senescenceassociated secretory phenotype (SASP).
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