Antimicrobial anxiety: the impact of stress on antimicrobial immunity

Leukocytes and epithelial cells are fundamental to antimi-crobial immunity. Their antimicrobial responses are an evolutionarily conserved component of the innate im-mune system and are influenced by the host’s response to external stimuli. The efficacy of host defense via anti-microbial responses derives from the ability of AMPs to rapidly identify and eradicate foreign microbes and acti-vate proinflammatory pathways, and from the capacity of later innate and adaptive immune responses to amplify protection through distinct biochemical mechanisms. Re-cent advances in neuroimmunology have identified a di-rect link between the neuroendocrine and immune sys-tems, where environmental stimuli are generally believed to promote a transient effect on the immune system in response to environmental challenges and are presum-ably brought back to baseline levels via neuroendocrine pathways. Stress is an environmental stimulus that flares from a variety of circumstances and has become en-grained in human society. Small bouts of stress are be-lieved to enhance the host’s immune response; however, prolonged periods of stress can be detrimental through excess production of neuroendocrine-derived mediators that dampen immune responses to invasive pathogens. Elucidation of the mechanisms behind stress-induced im-mune modulation of antimicrobial responses will ulti-mately lead to the development of more effective thera-peutic interventions for pathologic conditions. It is the in-tent of this review to broaden the existing paradigm of how stress-related molecules dampen immune re-sponses through suppression of antimicrobial mecha-nisms, and to emphasize that bacteria can use these fac-tors to enhance microbial pathogenesis during stress. J. Leukoc. Biol. 88: 000–000; 2010