Macrophages make me sick: How macrophage activation states influence sickness behavior

[摘要] The macrophage (M Phi) is an essential cellular first responder in the innate immune system, sensing, alerting, removing and destroying intrinsic and extrinsic pathogens. While congenital aplasia of granulocytes, Tar B lymphocytes leads to serious disease, lack of M Phi s is incompatible with life. The M Phi, however, is not a monomorphic entity. These constructers, repairers and defenders of the body are diverse in form and function. What controls M Phi phenotype is beginning to be understood and involves a complex interplay of origination, location and microenvironment. Common to all M Phi developmental pathways are pro-inflammatory and anti-inflammatory cytokines. M Phi s respond to these bioactives in distinct ways developing recently recognized activation phenotypes that canonically support bacterial clearance (classical activation), parasite defense/tissue repair (alternative activation) and anti-inflammation (deactivation). Critically, the same cytokines which orchestrate immune defense and homeostasis dramatically impact sense of well being and cognition by eliciting sickness symptoms. Such behaviors are the manifestation of pro/anti-inflammatory cytokine action in the brain and are a direct consequence of M Phi function. This review describes the new archetypal M Phi activation states, delineates microglia phenotypic plasticity and explores the importance of these macrophage activation states to sickness behavior. (C) 2011 Elsevier Ltd. All rights reserved.

[发布日期] 2011-11-01

[关键词] Microglia;Cytokine;Innate immunity;Immunobehavior;Neuroimmunity