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Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice

Hunzeker, John T.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1080588837

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Medical Microbiology and Immunology.
The immune system can be viewed as a diffuse sensory organ that is responsible for detecting and eliminating infiltrating pathogens. However, the immune system must strike a balance between limiting microbial replication and immune-induced pathology. The immune system has various regulatory mechanisms that can do this; one such immunoregulatory pathway is the bi-directional communication among the nervous, endocrine and immune system. Extrinsic factors, e.g. infection, and intrinsic factors, e.g. psychogenic stress, can activate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). Activation of these systems by either stress or infection leads to the secretion of glucocorticoids (GCs), catecholamines and opioids. Chronic elevation of GCs by restraint (RST) stress modulated the immune response to an experimental influenza A/PR8 viral infection. As demonstrated by experiments contained herein, RST altered cytokine gene expression, suppressed NK cell activity, and attenuated lymphocyte trafficking. Finally, RST enhanced viral replication (probably as a consequence of the RST mediated immunomodulation). Thus, alteration of normal immunoregulatory mechanisms by RST modulated the inflammatory, innate and adaptive response to an influenza A/PR8 viral infection. Previous studies from our laboratory using a social stress paradigm, social disruption (SDR), showed that SDR induced a state of functional GC resistance in cultured splenocytes. SDR, depending on the timing of the infection relative to the SDR cycle, differentially affected immune response to an influenza viral infection. When SDR occurred concurrently with the influenza infection, cytokine gene expression in the lung was suppressed at early time points during the infection. However, cytokine gene expression returned to control levels after SDR was stopped. In contrast, SDR prior to the influenza challenge attenuated the infection-induced weight loss and corticosterone secretion. Furthermore, lung IFN-β cytokine gene expression was increased concomitantly with decreased viral replication. These data demonstrated that the timing of SDR relative to the infection significantly altered the impact on the anti-viral immune response. SDR prior to influenza A/PR8 viral infection also altered the generation of immunological memory. Assessment of the delayed-type hypersensitivity (DTH) to influenza viral antigen revealed that SDR prior to infection enhanced the generation of immunological memory. Additionally, the severity of the infection following re-challenge attenuated in the previously stressed mice compared to immune control mice. Attenuated weight loss and corticosterone secretion occurred concurrently with reduced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α responses and decreased viral gene expression in the SDR mice. These data suggested that the experience of SDR prior to infection had a long term consequences on host susceptibility to a specific viral pathogen. Studies presented herein demonstrate that: 1) diverse psychological stressors differentially affect the immune system, 2) the timing of the stressor relative to the infection influences the impact on the immune response and 3) stress induced modulation of the primary response affects immunological memory. These findings revealed that neuroendocrine modulation of the immune system should be considered during disease treatment as well as during immunization protocols.
John Sheridan (Advisor)
Health Sciences, Immunology
Influeza Virus; Interleukins; Type I Interferons; Chemokines; Natural Killer Cells; Real-Time PCR; Murine; Inflammatory, Innate and Adaptive; Immune Memory; Social Disruption (SDR) Stress; Restraint (RST) Stress; HPA Axis; Flow Cytometry; Glucocorticoids

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Citations

  • Hunzeker, J. T. (2004). Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1080588837

    APA Style (7th edition)

  • Hunzeker, John. Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1080588837.

    MLA Style (8th edition)

  • Hunzeker, John. "Differential effects of stress on the immune response to influenza A/PR8 virus infection in mice." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1080588837

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.