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. 2014;6(6):716-26.
doi: 10.1159/000364945. Epub 2014 Aug 13.

M1 and M2 macrophages: the chicken and the egg of immunity

Charles D Mills  1 , Klaus Ley
Affiliations

M1 and M2 macrophages: the chicken and the egg of immunity

Charles D Mills et al. J Innate Immun. 2014.

Abstract

The purpose of this perspective is to describe a critical advance in understanding how immune responses work. Macrophages are required for all animal life: 'Inhibit' type macrophages in all animals (called M1) can rapidly kill pathogens, and are thus the primary host defense, and 'Heal' type macrophages (M2) routinely repair and maintain tissue integrity. Macrophages perform these activities in all animals without T cells, and also in T cell-deficient vertebrates. Although adaptive immunity can amplify macrophage polarization, the long-held notion that macrophages need to be 'activated' or 'alternatively activated' by T cells is incorrect; indeed, immunology has had it backward. M1/M2-type macrophages necessarily direct T cells toward Th1- or Th2-like activities, respectively. That such macrophage-innate activities are the central directing element in immune responses is a dramatic change in understanding how immune systems operate. Most important, this revelation is opening up whole new approaches to immunotherapy. For example, many modern diseases, such as cancer and atherosclerosis, may not display 'foreign' antigens. However, there are clear imbalances in M1/M2-type responses. Correcting such innate imbalances can result in better health. Macrophages are the chicken and the egg of immunity.

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Figures

Fig. 1
Fig. 1
a M1- or M2-dominant macrophages stimulate Th1- or Th2-like T cell responses that further amplify M1/M2-type responses. b The characteristic products and functions of M1/inhibit and M2/heal macrophage responses. Other products have been variously observed during both M1 and M2 responses. Mice do not have IL-8; their M1 macrophages express CXCL1 and CXCL2 instead. orn = Ornithine.
Fig. 2
Fig. 2
Macrophages initiate and direct virtually all immune responses. They are the center of the immune ‘Solar System’. CTL = Cytotoxic T lymphocyte.
Fig. 3
Fig. 3
Macrophages in vertebrates possess four basic functions that allow them to maintain host tissue homeostasis and respond to infectious or noninfectious threats in a variety of ways to optimize host protection. These functions are sample, heal, inhibit and present (antigen). CTL = Cytotoxic T lymphocyte.
See this image and copyright information in PMC

Comment in

  • The Janus face of macrophages in immunity.
    Herwald H, Egesten A. Herwald H, et al. J Innate Immun. 2014;6(6):713-5. doi: 10.1159/000367718. Epub 2014 Sep 10. J Innate Immun. 2014. PMID: 25322689 Free PMC article. No abstract available.

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