Age-associated inflammation and toll-like receptor dysfunction prime the lungs for pneumococcal pneumonia

E Hinojosa, AR Boyd, CJ Orihuela - The Journal of infectious …, 2009 - academic.oup.com
E Hinojosa, AR Boyd, CJ Orihuela
The Journal of infectious diseases, 2009academic.oup.com
Background Aging is associated with increased inflammation and risk of community-
acquired pneumonia. Streptococcus pneumoniae co-opts the nuclear factor κ B (NFkB)–
regulated proteins polymeric immunoglobulin receptor (pIgR) and platelet-activating factor
receptor (PAFr) to attach and invade cells. We sought to determine whether aging and
chronic inflammation were associated with increased pIgR and PAFr levels in the lungs and
increased susceptibility to S. pneumoniae infection Methods Lung protein and messenger …
Abstract
BackgroundAging is associated with increased inflammation and risk of community-acquired pneumonia. Streptococcus pneumoniae co-opts the nuclear factor κ B (NFkB)–regulated proteins polymeric immunoglobulin receptor (pIgR) and platelet-activating factor receptor (PAFr) to attach and invade cells. We sought to determine whether aging and chronic inflammation were associated with increased pIgR and PAFr levels in the lungs and increased susceptibility to S. pneumoniae infection
MethodsLung protein and messenger RNA levels were quantitated using Western blot and quantitative polymerase chain reaction. NFkB activation was measured by electrophoretic mobility shift assay. Cytokine levels were measured by cytometric bead analysis. To model chronic inflammation, mice were implanted with osmotic pumps that delivered tumor necrosis factor–α
ResultsAged mice and those infused with tumor necrosis factor–α had increased levels of pIgR and PAFr in their lungs and were more susceptible to S. pneumoniae infection. During pneumonia, aged mice had reduced levels of pIgR and PAFr and less NFkB activation, despite greater bacterial burden. We determined that aged mice had decreased amounts of lung Toll-like receptors 1, 2, and 4 and reduced capacity to respond to S. pneumoniae with proinflammatory cytokine production
ConclusionsAged mice and, potentially, elderly humans are more susceptible to pneumonia because of a priming effect of chronic inflammation and Toll-like receptor dysfunction
Oxford University Press