User:Immcarle53/sandbox

Article Evaluation
Needs additional citations for verification in the section "Role in adaptive immunity"

Addition of more content of the role in disease, "as a host for intracellular pathogens"

Majority of paragraph two goes without citation - possible citations needed

Maturation process needs more focus

I want to focus on adding depth to the macrophage page. The basic details (function, structure, location, etc.) seem to be well outlined and cited but the more detailed sections are not filled in significantly.

Drafting of Article
After reading the scientific study/article about intestinal macrophages, I went back to the macrophage page and realized there is slim to none said about the intestinal macrophage. Therefore, using that article as my main resource, I want to incorporate a section after "Tissue Macrophages" that focuses on the intestinal macrophage and how it compares to the macrophage primarily discussed in the page already.

Perhaps I will also still add to the disease portion of the page, depending on how much I am able to put into this new section for intestinal macrophages.

As a host for intracellular pathogens[edit]
In their role as a phagocytic immune cell macrophages are responsible for engulfing pathogens to destroy them. Some pathogens subvert this process and instead live inside the macrophage. This provides an environment in which the pathogen is hidden from the immune system and allows it to replicate.

Diseases with this type of behaviour include tuberculosis (caused by Mycobacterium tuberculosis) and leishmaniasis (caused by Leishmania species).

In order to minimize the possibility of becoming the host of an intracellular bacteria, macrophages have evolved defense mechanisms such as induction of nitric oxide and reactive oxygen intermediates, which are toxic to microbes. Macrophages have also evolved the ability to restrict the microbe's nutrient supply and induce autophagy.

I would like to continue on the role of macrophages becoming hosts to bacteria, as well and add onto the material I already added to the page.

Insert new 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 phenotypes to be altered by their environments. Like macrophages, intestinal macrophages are differentiated monocytes, though intestinal macrophages have to coexist with the 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.

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 TGF-β, which induces the change from proinflammatory macrophage to noninflammatory macrophage.

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 E. coli, but intestinal macrophages still do not release cytokines, even after phagocytosis. Also, intestinal macrophages do not express lipoplysaccharide (LPS), IgA, or IgG receptors. The lack of LPS receptors is important for the gut as the intestinal macrophages do not detect the microbe-associated molecular patterns (MAMPS/PAMPS) of the intestinal microbiome. Nor do they express IL-2 and IL-3 growth factor receptors.

Intestinal Macrophages 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. 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.