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Polarized Mφ1 and Mφ2 respond to alternative activation or exogenous danger signals, but not to IFNγ
Author(s) -
Gratchev Alexei,
Kzhyskowska Julia,
Koethe Kirsten,
MullerMolinet Isabelle,
Kannookadan Sheila,
Utkial Jochen,
Goerdt Sergij
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb122-d
Subject(s) - immune system , cytokine , population , microbiology and biotechnology , immunology , secretion , stimulation , macrophage , biology , chemistry , neuroscience , medicine , endocrinology , in vitro , biochemistry , environmental health
Macrophages (Mϕ) represent a versatile cell population that develops and operates under the influence of a changing microenvironment to induce, regulate and restrict immune reactions. In parallel to the Th1/Th2 dichotomy, the extremes of a continuum of macrophage functional states have been termed classically (Mϕ1) and alternatively (Mϕ2) activated macrophages. In this study, we investigated the functional plasticity of polarized human Mϕ in response to a stimulation by Th1 (IFNγ) or Th2 (IL‐4, IL‐10) cytokines or by exogenous danger signals (LPS, MDP). Mϕ1 IFNγ underwent alternative activation by IL‐4 and IL‐10 as demonstrated by de novo secretion of the Th2‐associated cytokines AMAC‐1 and IL‐1ra. Vice versa, Mϕ2 and Mϕ1 IFNγ underwent classical activation in response to LPS and MDP by producing the Th1‐associated cytokines IL‐1β and TNFα, while both populations were refractory to IFNγ. Expression of the Th1‐inducing cytokine IL‐12 was induced by LPS in all macrophage populations except for Mϕ1 IFNγ . The ability of polarized Mϕ to react to alternative activation and exogenous danger signals is a precondition for the immune system to reliably down‐regulate an outdated immune reaction and at the same time to retain the capacity to instantaneously mount a response towards a bacterial infection; refractoriness to IFNγ may contribute to prevent the development of autoimmunity.