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Global analyses of monocyte subsets revealed age-related alternations after stimulation of pathogen recognition receptors
Journal article   Peer reviewed

Global analyses of monocyte subsets revealed age-related alternations after stimulation of pathogen recognition receptors

Talibah Metcalf, Peter Wilkinson, Anne Wertheimer, Janko Nikolich-Zugich and Elias Haddad
The Journal of immunology (1950), v 196(1_Supplement), pp 60-60.20
01 May 2016
DOI: https://doi.org/10.4049/jimmunol.196.Supp.60.20

Abstract

Abstract In the aging population, intricate interactions between the innate and adaptive immune response is not as effective compared to younger adults. Monocytes play an important role in defense against microbes and express an array of pattern recognition receptors (PRRs). We applied a comprehensive approach to evaluate the effects of a broad range of innate immune agonists (LPS, CLO97, and 5′pppRNA) on monocyte subsets isolated from healthy non-frail adults and old subjects. We analyzed transcriptome data and measured cytokine and chemokine, ROS, and NO production. Under ex vivo conditions, we observed a larger proportion of genes were specifically upregulated in the classical (CD14+CD16−) and non-classical (CD14dimCD16+) monocytes while the intermediate (CD14+CD16+) monocytes showed a smaller proportion of upregulated genes. Distinct genes observed across both age groups for CD16+ monocytes included: CX3CR1, IL21R, IFITM1/2/3, SIGLEC10, and SOD1; whereas CD16− monocytes expressed CCR1/2, SELL, CD64, CD93, CD36, and CD14. Analysis of the transcriptional profiles elicited by innate agonists revealed age-related alternations in functional pathways. After stimulation of RIGI with 5′pppRNA, we observed that classical monocytes isolated from adults uniquely expressed the RIGI MDA5 mediated induction of IFNα and IFNβ pathway, as well as the IFNα transcript, which corresponded to higher levels of IFNα production. In addition, agonists elicited higher levels of IFNγ from non-classical monocytes isolated from adults. Our findings represent a comprehensive analysis of the influence of human aging on PRRs signaling and have implications for strategies to enhance the immune response in the context of infection or immunization.

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