Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
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Edited by Burton H. Singer, University of Florida, Gainesville, FL, and approved October 21, 2015 (received for review July 21, 2015)
Significance
Perceived social isolation (PSI) (loneliness) is linked to increased risk of chronic disease and mortality, and previous research has implicated up-regulated inflammation and down-regulated antiviral gene expression (the conserved transcriptional response to adversity; CTRA) as a potential mechanism for such effects. The present studies used integrative analyses of transcriptome regulation in high-PSI humans and rhesus macaques to define the basis for such effects in neuroendocrine-related alterations in myeloid immune cell population dynamics. CTRA up-regulation also preceded increases in PSI, suggesting a reciprocal mechanism by which CTRA gene expression may both propagate PSI and contribute to its related disease risks.
Abstract
To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14++/CD16− classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.
Footnotes
- ↵1To whom correspondence should be addressed. Email: Cacioppo{at}uchicago.edu.
Author contributions: S.W.C., J.P.C., and J.T.C. designed research; S.W.C., J.P.C., K.C., J.M.G.A., J.M., and J.T.C. performed research; S.W.C. contributed new reagents/analytic tools; S.W.C., J.P.C., and J.T.C. analyzed data; and S.W.C., J.P.C., and J.T.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession nos. GSE65213, GSE65298, GSE65317, GSE65341, GSE65403, and GSE65243).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1514249112/-/DCSupplemental.
Freely available online through the PNAS open access option.
Myeloid differentiation in social isolation
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