Stress responses have been associated with altered immunity and depending upon the type of stressor, can have diverse effects on disease outcomes. As the first line of defense against potential pathogens, alterations in cellular immune responses along the respiratory tract can have a significant impact on the manifestation of local and systemic disease. Utilizing a murine model of respiratory pneumonia, the current study investigated the effects of restraint stress on the induction of primary and secondary immunity along the respiratory tract, influencing host susceptibility. Female CD-1 mice were subjected to three hours of restraint stress over a period of four days followed by primary and secondary Streptococcus pneumoniae infection via intranasal route. Stress exposure led to increased retention of bacterial carriage in the lungs, enhanced polymorphonuclear cells and a preferential decrease in pulmonary CD11c(+) MHC II(+) cells resulting in delayed lethality during primary infection but significant impairment of acquired immune protection after secondary infection. We also provide evidence to support a role for lung-associated corticotropin releasing hormone regulation through peripheral CRH and diverse CRH receptor expression by MHC II(+) antigen presenting cells (APCs). We conclude that repeated restraint stress has distinct influences on immune cell populations that appear to be important in the generation of innate and adaptive immune responses along the respiratory tract with the potential to influence local and systemic protection against disease pathogenesis.
Epidemiological and experimental studies suggest a positive correlation between chronic respiratory inflammatory disease and the ability to cope with adverse stress. Interactions between neuroendocrine and immune systems are believed to provide insight toward the biological mechanisms of action. The utility of an experimental murine model was employed to investigate the immunological consequences of stress-controllability and ovalbumin-induced airway inflammation. Pre-conditioned uncontrollable stress exacerbated OVA-induced lung histopathological changes that were typical of Th2-predominant inflammatory response along respiratory tissues. Importantly, mice given the ability to exert control over aversive stress attenuated inflammatory responses and reduced lung pathology. This model represents a means of investigating the neuro-immune axis in defining mechanisms of stress and respiratory disease.
Asthma is becoming more prevalent in today's world, particularly prevalent among children. Africans American children are more to susceptible to asthma than white Americans. It is becoming increasingly clear that stress is a major risk factor for asthma. Though asthma and stress has a very strong relationship, we still lack a clear understanding the of underlying mechanisms through which stress influences disease pathogenesis. Asthma has been described as psychosomatic disorder. As the pulmonary immune system is under the control of the Central Nervous system (CNS) and endocrine system, dys‐regulation in this system may be a contributing factor in immune mediated exacerbation of asthma. Our current focus is to understand how signaling events between brain, an immune privileged organ can control disease severity along the respiratory tract. To investigate the effects of stress on asthma severity, ovalbumin sensitized mice were exposed to an experimental stress paradigm involving control and uncontrolled stress conditions. Our preliminary data has shown that significant changes in behavioral patterns between the conditions that corresponded with immune dys‐regulation that corresponded immune mediated severity of asthma. We also demonstrate cortocotrophin Realeasing Hormone (CRH) expression level in the lung is associated with differences in the disease severity of asthma. Such differences suggest that stress may be a contributing factor in regulation of Antigen Presenting Cells, the key player in innate immune system. We have seen accumulation and of these cells in the lungs. We hypothesize that stress induced alteration in APC function will dictate pro‐asthmatic immune response. This link can lead us to functioning of these immune cells in the case of asthma. These findings can have the implications for treatment of Th2 mediated disease such as asthma.
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