M phi 1 and M phi 2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals

Macrophages (M phi) represent a dynamic cell population that develops and operates within a changing microenvironment. in parallel to Th1/Th2 cells, primary M phi may undergo classical (M phi 1) or alternative (M phi 2) activation. Here, we investigated whether M phi 1/M phi 2 may be re-polarized by a secondary stimulation by Th1 or Th2 cytokines or by exogenous danger signals. We established that M phi 1(IFN gamma) respond to alternative activation by IL-4 and IL-10 by de novo secretion of Th2 cytokines AMAC-1 and IL-1ra, and by an increase in phagocytic capacity and a decrease in bactericidal activity. Vice versa, M phi 2 responded to classical activation by IFN gamma exhibiting reduced phagocytosis and significantly increased bacterial killing while being refractory regarding secretion of TNF alpha, IL-1 beta and IL-12. In response to the bacterial danger signals LPS and MDP, both M phi 1 and M phi 2 produced IL-1 beta and TNF alpha; in addition M phi 2 expressed the Th1-inducing cytokine IL-12. The ability of M phi to be re-polarized and to react to exogenous danger signals is a precondition to down-regulate an outdated immune reaction and to retain the capacity to mount an adequate anti-bacterial response. Selective refractoriness of M phi 1 and M phi 2 to IFN gamma- and LPS-induced cytokine secretion may contribute to prevent autoimmunity. (c) 2006 Elsevier GmbH. All rights reserved.