The Type I interferon antiviral gene program is impaired by lockdown and preserved by caregiving

Abstract

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic “shelter in place” (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16− classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.

Human social genomics: Concepts, mechanisms, and implications for health

“…54 Similar results emerged from subsequent studies modeling the effects of COVID-19 pandemic-style "shelterin-place" protocols in nonhuman primates, with macaques relocated from social housing to two weeks of individual housing again showing increased pro-inflammatory activity and reduced antiviral activity. 27 These results are consistent with the hypothesis that social processes cause alterations in gene expression in primates and, importantly, these primate results mirror what has been found in humans exposed to social isolation and other forms of social-environmental adversity.…”

“…The biochemical signaling pathways that regulate human gene expression are now also known to be influenced by both physical and social-environmental conditions. Social isolation, for example, has been related to the differential expression of hundreds of genes [24][25][26][27][28] that impact immune function as well as behavioral phenotypes. 25,29 Given that our cells have an average half-life of about 80 days and are constantly being replaced, these dynamics provide insight into how a social factor such as social isolation can get under the skin, so to speak, to influence human health and behavior for years to come.…”

Psychic Life-Biological Molecule Bidirectional Relationship: Pathways, Mechanisms, and Consequences for Medical and Psychological Sciences—A Narrative Review

“…This immune-dysregulated pattern is called “conserved transcriptional response to adversity” because it tends to stabilize across time and has been found in a wide series of life adversities, including low socioeconomic status, social isolation, and breast cancer recurrence. In contrast, prosocial engagement and non-stressing caregiving reduce inflammatory gene expression and increase anti-viral response [ 76 , 77 ].…”

Psychoneuroimmunology in the time of COVID-19: Why neuro-immune interactions matter for mental and physical health

“…One recent study used a nonhuman primate model to examine the immune effects of “shelter in place” (SIP) policies, which have been widespread during the pandemic, and how social interaction may ameliorate these effects ( Cole et al, 2021 ). Adult male rhesus macaques were moved from communal field cage communities to individual indoor shelters for two weeks, which led to pronounced decreases in Type I interferon gene expression.…”