Editing Macrophage (section)

== Intestinal macrophages ==
Though very similar in structure to tissue macrophages, intestinal macrophages have evolved specific characteristics and functions given their natural environment, which is in the digestive tract. Macrophages and intestinal macrophages have high plasticity causing their phenotype to be altered by their environments.<ref>{{cite journal | vauthors = Kühl AA, Erben U, Kredel LI, Siegmund B | title = Diversity of Intestinal Macrophages in Inflammatory Bowel Diseases | journal = Frontiers in Immunology | volume = 6 | pages = 613 | date = 2015-12-07 | pmid = 26697009 | pmc = 4670857 | doi = 10.3389/fimmu.2015.00613 | doi-access = free }}</ref> Like macrophages, intestinal macrophages are differentiated monocytes, though intestinal macrophages have to coexist with the [[Microbiota|microbiome]] in the intestines. This is a challenge considering the bacteria found in the gut are not recognized as "self" and could be potential targets for phagocytosis by the macrophage.<ref name="Smythies-2005">{{cite journal | vauthors = Smythies LE, Sellers M, Clements RH, Mosteller-Barnum M, Meng G, Benjamin WH, Orenstein JM, Smith PD | title = Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity | journal = The Journal of Clinical Investigation | volume = 115 | issue = 1 | pages = 66–75 | date = January 2005 | pmid = 15630445 | pmc = 539188 | doi = 10.1172/JCI19229 }}</ref>

To prevent the destruction of the gut bacteria, intestinal macrophages have developed key differences compared to other macrophages. Primarily, intestinal macrophages do not induce inflammatory responses. Whereas tissue macrophages release various inflammatory cytokines, such as IL-1, IL-6 and TNF-α, intestinal macrophages do not produce or secrete inflammatory cytokines. This change is directly caused by the intestinal macrophages environment. Surrounding intestinal epithelial cells release [[Transforming growth factor beta|TGF-β]], which induces the change from proinflammatory macrophage to noninflammatory macrophage.<ref name="Smythies-2005" />

Even though the inflammatory response is downregulated in intestinal macrophages, phagocytosis is still carried out. There is no drop off in phagocytosis efficiency as intestinal macrophages are able to effectively phagocytize the bacteria,''S. typhimurium'' and ''[[Escherichia coli|E. coli]]'', but intestinal macrophages still do not release cytokines, even after phagocytosis. Also, intestinal macrophages do not express lipopolysaccharide (LPS), IgA, or IgG receptors.<ref name="Mowat-2011">{{cite journal | vauthors = Mowat AM, Bain CC | title = Mucosal macrophages in intestinal homeostasis and inflammation | journal = Journal of Innate Immunity | volume = 3 | issue = 6 | pages = 550–564 | date = 2011 | pmid = 22025201 | pmc = 3224516 | doi = 10.1159/000329099 }}</ref> The lack of LPS receptors is important for the gut as the intestinal macrophages do not detect the microbe-associated molecular patterns [[Pathogen-associated molecular pattern|(MAMPS/PAMPS)]] of the intestinal microbiome. Nor do they express IL-2 and IL-3 growth factor receptors.<ref name="Smythies-2005" />

=== Role in disease ===

Intestinal macrophages have been shown to play a role in [[inflammatory bowel disease]] (IBD), such as [[Crohn's disease]] (CD) and [[ulcerative colitis]] (UC). In a healthy gut, intestinal macrophages limit the inflammatory response in the gut, but in a disease-state, intestinal macrophage numbers and diversity are altered. This leads to inflammation of the gut and disease symptoms of IBD. Intestinal macrophages are critical in maintaining gut [[homeostasis]]. The presence of inflammation or pathogen alters this homeostasis, and concurrently alters the intestinal macrophages.<ref>{{cite journal | vauthors = Bain CC, Mowat AM | title = Macrophages in intestinal homeostasis and inflammation | journal = Immunological Reviews | volume = 260 | issue = 1 | pages = 102–117 | date = July 2014 | pmid = 24942685 | pmc = 4141699 | doi = 10.1111/imr.12192 }}</ref> There has yet to be a determined mechanism for the alteration of the intestinal macrophages by recruitment of new monocytes or changes in the already present intestinal macrophages.<ref name="Mowat-2011" />

Additionally, a new study reveals macrophages limit iron access to bacteria by releasing extracellular vesicles, improving sepsis outcomes.<ref>{{cite journal | vauthors = Weiss G | title = Macrophage vesicles starve bacteria of iron | journal = Nature Metabolism | volume = 5 | issue = 1 | pages = 10–12 | date = January 2023 | pmid = 36658401 | doi = 10.1038/s42255-022-00719-1 | s2cid = 256030791 }}</ref>