Resilience and immunity

Abstract

Resilience is the process that allows individuals to adapt to adverse conditions and recover from them. This process is favored by individual qualities that have been amply studied in the field of stress such as personal control, positive affect, optimism, and social support. Biopsychosocial studies on the individual qualities that promote resilience show that these factors help protect against the deleterious influences of stressors on physiology in general and immunity in particular. The reverse is also true as there is evidence that immune processes influence resilience. Most of the data supporting this relationship comes from animal studies on individual differences in the ability to resist situations of chronic stress. These data build on the knowledge that has accumulated on the influence of immune factors on brain and behavior in both animal and human studies. In general, resilient individuals have a different immunophenotype from that of stress susceptible individuals. It is possible to render susceptible individuals resilient and vice versa by changing their inflammatory phenotype. The adaptive immune phenotype also influences the ability to recover from inflammation-induced symptoms. The modulation of these bidirectional relationships between resilience and immunity by the gut microbiota opens the possibility to influence them by probiotics and prebiotics. However, more focused studies on the reciprocal relationship between resilience and immunity will be necessary before this can be put into practice.

Keywords: CD8 T cells; Cytokines; Depression; Gut microbiota; Gut-brain axis; Immunity; Indoleamine 2,3 dixoygenase; Inflammation; Optimism; Personal control; Positive affect; Psychobiotics; Recovery; Resilience; Social support; Stress.

Fig. 1

A heuristic model of how stressful life events can influence immunity and health (downward arrows), the potential feedback of excessive inflammation on the process (curved arrows), and the points at which psychological resilience factors can short-circuit this process (horizontal arrows). Adapted from Cohen et al. (2016).

Fig. 2

Mechanisms of inflammation-induced depression and its recovery. Systemic inflammation in response to infection, ‘leaky’ gut or stress activates indoleamine 2,3 dioxygenase (IDO1) and induces the expression of inflammatory mediators by brain macrophages and microglia. Activation of IDO1 leads to the increased formation of kynurenine. Circulating kynurenine is transported through the blood-brain barrier and converted into neurotoxic kynurenine metabolites by enzymes mainly expressed in microglia. Somatic symptoms of depression are the result of the action of brain inflammatory mediators on neuronal networks regulating arousal and incentive motivation. Cognitve/affective symptoms of depression are mediated in part by the action of neurotoxic kynurenine metabolites on glutamatergic neurotransmission. Activation of brain macrophages and microglia recruits CD8-positive T cells into the meninges and choroid plexus. These T cells switch brain macrophages and microglia into an anti-inflammatory phenotype that is pivotal for the recovery process. Note the blue color for the mechanism that lead from inflammation to depression and the red color for the mechanisms that promote recovery. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Schematic depicting effects of chronic stress on endothelial barrier. Chronic social defeat stress in mice and depression in humans is associated with increased circulating levels of leukocytes (largely monocytes and neutrophils) and reduced expression of the tight junction protein claudin-5 (CLDN5). In mice loss of CLDN5 results in an opening of the blood brain barrier that allows circulating inter-leukin-6 (IL-6) to directly enter the brain where it might act on astrocytes (depicted by red cells in the brain) or microglia (depicted by white cells in the brain) within mood related structures such as the nucleus accumbens to increase depression-like behaviors compared to resilient and control mice. Although, untested, there may be alterations in astrocytes or microglia induced by peripheral IL-6 infiltration that further promote blood-brain barrier permeability and/or neuroinflammation. Adapted with permission from Menard et al. (2017).

Fig. 4

Role of the gut microbiota in gut-to-brain signaling in health with high resilience and in depression with an exaggerated stress response. The communication between gut and brain is bidirectional. Stress can lead to gut dysbiosis and in turn dysbiosis can result in central changes leading to decreased resilience with vulnerability to depression. As can be seen, Chao 1 species richness is decreased in depression.