Social Stress-induced Increases in NK Cell Cytolytic Potential Without Infection

Natural killer (NK) cells are innate lymphocytes that serve as primary mediators in the early defense against viral challenges such as HSV-1.  Many factors including stress increase the severity and susceptibility to a variety of viruses.  However, social disruption (SDR) stress has unique characteristics that maybe beneficial in studying pathogenic resistance.  For example, SDR causes prolonged HPA-axis and sympathetic nervous system activation resulting in glucocorticoid resistant immune cells.  In addition, these neuroendocrine meditated changes have dramatic effects on immunological resistance to bacterial and viral infections through increased innate immune cell “priming”, trafficking, cytokine and chemokine production. 

Objective: To determine if an SDR-induced altered microenvironment has a similar “priming” effect on NK cells in a pathogen free model as it does with other immunological cell types (e.g., macrophages/monocytes).

Methods: Mice were subjected to 6 consecutive days of SDR (2 hrs/night).  Fourteen hours after the last cycle of SDR, lung and spleen tissue were collected, processed, and quantified by flow cytometry for activation, inhibitory, and cytolytic markers. Additionally, isolated splenic-derived NK cells were stimulated ex vivo with IgG and IL-2.  Following a 48 hr incubation, supernatants were collected and IFNγ was measured by ELISA.

Results: Results indicate SDR alone is capable of increasing activating receptors, and differentially reducing inhibitory receptor surface expression on lung and splenic NK cells. Furthermore, SDR increased cytolytic potential evidenced by increased expression of CD107a on NK cells both in the lung and spleen and increased IFNγ production in response to isolated NK stimulation.  

Conclusion: These data show that SDR in the absence of infection is able to “prime” NK cells similar to other innate immune cells by increasing activation, decreasing inhibition, and increasing cytolytic potential. Mechanisms found in these studies may lead to therapeutic approaches to prevent viral infection, recurrence, severity, and transmission in susceptible patients.