Feng Qian1, Xiaomei Wang1, Lin Zhang1, Shuqing Chen2, Marta Piecychna1, Heather Allore2, Linda K. Bockenstedt1, Stephen E. Malawista1, Richard Bucala1, Albert C. Shaw3, Erol Fikrig4,5, Ruth R. Montgomery1
1Section of Rheumatology
2Program on Aging
3#N# #N# Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine,
4Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine
5The Howard Hughes Medical Institute, 300 Cedar Street, New Haven, CT 06520, USA
Tóm tắt
SummaryAging 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.
