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

Aging Cell. 2012 Feb;11(1):104-10. doi: 10.1111/j.1474-9726.2011.00759.x. Epub 2011 Nov 28.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology
  • Aging / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / immunology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Multivariate Analysis
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Phosphorylation
  • Protein Transport
  • RNA, Messenger / biosynthesis*
  • Signal Transduction / immunology
  • Toll-Like Receptor 5 / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Interleukin-8
  • NF-kappa B
  • RNA, Messenger
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • Tumor Necrosis Factor-alpha
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases