Summary Aging is accompanied by a progressive decline in immune function. Studies have shown age‐related decreases in the expression and signaling efficiency of Toll‐like receptors (TLRs) in monocytes and dendritic cells and dysregulation of macrophage TLR3. Using a multivariable mixed effect model, we report a highly significant increase in TLR5‐induced production of IL‐8 from monocytes of older individuals (P < 0.0001). Elevated IL‐8 is accompanied by increased expression of TLR5, both protein and mRNA, and by increased levels of TLR5‐mediated phosphorylation of MAPK p38 and ERK. We noted incomplete activation of NF‐κB in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF‐α. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.
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Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian, Feng; Wang, Xiaomei; Zhang, Lin; Chen, Shu; Piecychna, Marta; Allore, Heather; Bockenstedt, Linda; Malawista, Stephen; Bucala, Richard; Shaw, Albert C.; Fikrig, Erol; Montgomery, Ruth R.
Follow Aging Cell
, Volume 11 (1)
Wiley – Feb 1, 2012
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