Journal
JOURNAL OF INNATE IMMUNITY
Volume 6, Issue 6, Pages 716-726Publisher
KARGER
DOI: 10.1159/000364945
Keywords
M1 and M2 macrophages; Innate immunity; Wound healing; Arginase; Nitric oxide
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL115232] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL115232] Funding Source: Medline
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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. (C) 2014 S. Karger AG, Basel
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