Mφ1 and Mφ2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals

Macrophages (Mφ) represent a dynamic cell population that develops and operates within a changing microenvironment. In parallel to Th1/Th2 cells, primary Mφ may undergo classical (Mφ1) or alternative (Mφ2) activation. Here, we investigated whether Mφ1/Mφ2 may be re-polarized by a secondary stimulation by Th1 or Th2 cytokines or by exogenous danger signals. We established that Mφ1IFNγ 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, Mφ2 responded to classical activation by IFNγ exhibiting reduced phagocytosis and significantly increased bacterial killing while being refractory regarding secretion of TNFα, IL-1β and IL-12. In response to the bacterial danger signals LPS and MDP, both Mφ1 and Mφ2 produced IL-1β and TNFα; in addition Mφ2 expressed the Th1-inducing cytokine IL-12. The ability of Mφ to be re-polarized and to react to exogenous danger signals is a precondition to down-regulate an outdated immune reaction and to retain the capacity to mount an adequate anti-bacterial response.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 Mφ1 and Mφ2 to IFNγ- and LPS-induced cytokine secretion may contribute to prevent autoimmunity.