Age-related alterations in innate immune receptor expression and ability of macrophages to respond to pathogen challenge in vitro

The impact of ageing in innate immunity is poorly understood. Studies in the mouse model have described altered innate immune functions in aged macrophages, although these were not generally linked to altered expression of receptors or regulatory molecules. Moreover, the influence of ageing in the expression of these molecules has not been systematically examined. We investigated age-dependent expression differences in selected Toll-like and other pattern-recognition receptors, receptors involved in inflammatory amplification, and in transmembrane and intracellular regulators of inflammatory signaling. Young and aged macrophages were examined under resting conditions or upon activation with Porphyromonas gingivalis, a major pathogen in periodontal disease, the prevalence and severity of which increase in old age. We detected a limited number of age-dependent alterations, involving both reduction and increase of immune activity. Interestingly, surface expression of receptors that amplify inflammation (C5a anaphylatoxin receptor and triggering receptor expressed on myeloid cells [TREM]-1) was elevated in aged macrophages. No significant age-dependent differences were observed regarding the phagocytosis and intracellular killing of P. gingivalis, consistent with lack of significant changes in phagocytic receptor expression and induction of antimicrobial molecules. Therefore, at least at the cellular level, certain aspects of innate immune function may not necessarily decline with age.