Mphi1 and Mphi2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals.
Macrophages (Mphi) represent a dynamic cell population that develops and operates within a changing microenvironment. In parallel to Th1/Th2 cells, primary Mphi may undergo classical (Mphi1) or alternative (Mphi2) activation. Here, we investigated whether Mphi1/Mphi2 may be re-polarized by a secondary stimulation by Th1 or Th2 cytokines or by exogenous danger signals. We established that Mphi1IFNgamma 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, Mphi2 responded to classical activation by IFNgamma exhibiting reduced phagocytosis and significantly increased bacterial killing while being refractory regarding secretion of TNFalpha, IL-1beta and IL-12. In response to the bacterial danger signals LPS and MDP, both Mphi1 and Mphi2 produced IL-1beta and TNFalpha; in addition Mphi2 expressed the Th1-inducing cytokine IL-12. The ability of Mphi to be re-polarized and to react to exogenous danger signals is a precondition to down-regulate an outdated immune reaction and to retain the capacity to mount an adequate anti-bacterial response.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 Mphi1 and Mphi2 to IFNgamma- and LPS-induced cytokine secretion may contribute to prevent autoimmunity.
Gratchev
Alexei
A
Department of Dermatology, University Medical Centre Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany. alexei.gratchev@haut.ma.uni-heidelberg.de
Kzhyshkowska
Julia
J
Köthe
Kirsten
K
Muller-Molinet
Isabelle
I
Kannookadan
Sheila
S
Utikal
Jochen
J
Goerdt
Sergij
S
D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology* / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology
D016207:Cytokines; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine