Editors' ChoiceAging

Inflamm-vestigating inflamm-aging

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Science Translational Medicine  26 Jul 2017:
Vol. 9, Issue 400, eaao0973
DOI: 10.1126/scitranslmed.aao0973


Monocytes from elderly people respond differently to pattern recognition receptor engagement than monocytes from younger adults.

For some infectious diseases, the burden of disease is much higher for the elderly, with increased risks of hospitalization and death. The mechanisms for the differences in susceptibility are being investigated, as in a recent publication by Metcalf et al. They studied how monocyte subsets from blood of older people (mean 73 years) respond to engagement of pattern recognition receptors, compared with monocytes from a younger adult cohort (mean 30 years). They included non-frailty, living independently, and non-dementia as entrance criteria for the older age group. Controlled hypertension, diabetes, and arthritis and concurrent medications other than corticosteroids were not exclusion criteria.

The authors isolated classical, nonclassical, and intermediate monocytes from peripheral blood using negative selection and cell sorting; prior studies have documented distinct cytokine profiles in these groups. The monocytes were treated with TLR4, TLR7/8, and retinoic acid–inducible gene I agonists to simulate innate immune response to bacteria (LPS) and viruses (CLO97 derivative of imidazoquinoline and dsRNA). Responses to these TLR agonists were assessed by analyzing gene transcription using microarray, cytokine levels using a multiplex bead assay, and receptor expression using flow cytometry.

Some proinflammatory molecules were increased in the older age group’s monocytes. One example is CX3C chemokine receptor 1 (CX3CR1), which interacts with its ligand to increase trafficking to tissues. Monocyte cell surface expression of CX3CR1 was higher in untreated classical and nonclassical blood monocytes from the older compared with the younger group. If this corresponds to differential levels in the tissues, CX3CR1 could be contributing to chronic inflammatory conditions more common with increasing age. In nonclassical monocytes from adults, there was about twice the amount of interferon-γ (IFN-γ) after stimulation with LPS or CLO97 compared with nonclassical monocytes from the older age group. Additionally, IFN-α transcript and cytokine levels were higher in classical monocytes from adults treated with dsRNA. IFN-γ and IFN-α response to specific pathogenic antigens in monocyte subsets of the elderly is an area for future study, which could have implications for our understanding of differential susceptibility to certain infections in older age groups. Additionally, discovery of mechanisms for how chronic inflammation and decreased inflammatory response to pathogens coexist will be essential for development of potential interventions.

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