English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Macrophages are the epicenter of all immune systems (1). The first and the most abundant leukocyte observed (2), macrophage have long been relegated to the role of “servants” of T or B cells/adaptive immunity. This view is now known to be backward. Macrophages necessarily initiate and direct virtually all immune responses from simple multicellular animals to humans.  There is good news and bad news in the newly recognized importance of macrophages/innate immunity. The well-known “double-edged sword” nature of the immune system can largely be attributed to macrophages’ unique ability to make polar-opposite repair/heal (M2) or kill/inhibit (M1) type responses (3).  In health, M2-type macrophages maintain homeostasis by helping repair and replace lost or effete cells. Ever-present in tissues, macrophages are also the primary host defense against pathogens (or altered self cells) because their unique physiology allows them to rapidly switch from their M2/heal mode to an M1/inhibit mode: both powerful responses; both potentially dangerous.  In disease, over expression of M2/heal macrophages contributes to chronic infections, fibrosis, allergy, and cancer (3). Conversely, M1/inhibit-dominant activity plays a major role in atherosclerosis, autoimmunity, and other chronic inflammatory conditions.  Of fundamental importance is that both the routine M2/heal and the induced M1/inhibit macrophage functions occur in all animals whether they have T cells or not. Furthermore, M1 and M2 macrophage responses play necessary roles in causing T cells to make Th1 or Th2-type responses if pathogens or altered self are present (4). Hence, the renaming of macrophage responses M1 and M2.  This new knowledge about the central role of macrophages in immune systems brings great promise for increasing health/decreasing disease. In this regard, the ability of macrophages to exhibit the polar-opposite M2/heal and M1/kill functions result, in part, from their unique ability to metabolize one amino acid – arginine – to either growth-promoting ornithine or growth-inhibiting nitric oxide (NO) (5). Hence, the title of this Topic, “M1 and M2 Macrophages: The Arginine Fork in the Road to Health and Disease.” We hope that the articles assembled here help illuminate the basic functions of macrophages referred to as SHIP [sample, heal, inhibit, and present (antigen)]. Such knowledge is critical for developing the means to modulate the direct M2/heal or M1/inhibit responses of macrophages, or their indirect abilities to initiate and direct T and B cell responses. One can properly say macrophages are the “chicken and the egg” of immunity (1).

Macrophages at the Fork in the Road to Health or Disease