The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens


The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.

Publication DOI:
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > Aston Pharmacy School
Additional Information: © 2010 British Society for Immunology.
Uncontrolled Keywords: aging,animals,bacteria,humans,macrophages,immunological models,signal transduction,toll-like receptors,viruses,Immunology,Immunology and Allergy
Publication ISSN: 1365-2249
Last Modified: 19 Jun 2024 07:09
Date Deposited: 25 May 2012 10:38
Full Text Link: http://onlineli ... 4213.x/abstract
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2010-09
Published Online Date: 2010-07-14
Authors: Dunston, Christopher
Griffiths, Helen R. (ORCID Profile 0000-0002-2666-2147)



Version: Published Version

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