Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly

作者：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^*

来源：AGING CELL, 2012, 11(1): 104-110.

DOI：10.1111/j.1474-9726.2011.00759.x

• aging
• toll-like receptors
• monocytes
• immunosenescence
• IL-8
• flagellin

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-?B in response to TLR5 signaling in monocytes of elderly donors, as reflected by the absence of an associated increase in the production of TNF-a. Elevated TLR5 may provide a critical mechanism to enhance immune responsiveness in older individuals.

• 出版日期2012-2