Immunity and Infectious Illness Role of Macrophage Cytokines

Kelly Nim^*
*Correspondence: Kelly Nim, Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, 34141, Daejeon, Republic of Korea, Email:

Editorial

Macrophages have evolved to become essential for both development and immunity. Their duties include everything from forming body plans to ingesting and getting rid of infections and apoptotic cells. Small, soluble proteins called cytokines facilitate communication and provide instructions to immune and non-immune cells. A variety of cytokines play a crucial role in macrophages' capacity to act as innate immune system sentinels and mediate the switch from innate to adaptive immunity. Together with other mediators, cytokines influence the fate of macrophages, which can range from those that promote inflammation when they are "classically activated" to those that are anti-inflammatory or "alternatively activated."

Deregulated cytokine secretion has been linked to a number of illness conditions, including allergies and chronic inflammation. Macrophages release cytokines through a number of exquisitely coordinated spatiotemporally controlled mechanisms. Multi-protein complexes that direct cytokines from their place of synthesis to their ports of exit into the extracellular milieu coordinate various exocytic cytokine secretion routes at the molecular level [1].

Macrophages are innate immune system phagocytic cells found in a variety of organs. Elie Metchnikoff, a Russian scientist, was awarded the 1908 Nobel Prize in Physiology or Medicine for his research on immunity after noticing that a population of cells moved to the wound after he punctured starfish larvae. Additionally, he noticed cells that could take up particles that had been inserted in the larvae's digestive systems. These cells were first known as phagocytes by Elie Metchnikoff, who later referred to them as white blood cells due to their first line of defence against infection in living things. The reticuloendothelial system was replaced by the idea of the mononuclear phagocyte system, which is made up of various macrophages produced from bone marrow monocytes. Most bone marrow precursor cells that become monocytes give rise to macrophages. These develop from granulocytic-monocytic stem cells in the bone marrow after being exposed to cytokines such granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3). Expression of certain membrane cytokine receptors is related to differentiation from stem cells.

Monocytes stay in the bone marrow for less than 24 hours before entering the bloodstream and travelling throughout the entire body. The half-life of a circulating monocyte in healthy, normal humans is thought to be 70 hours. Monocytes make up 1%–6% of all leukocytes in normal peripheral blood. Monocytes develop into macrophages after navigating connective tissue's capillary walls. The cell grows between five and ten times in size, its organelles multiply in quantity and complexity, its phagocytic capacity rises, among other modifications, during this differentiation process. It is significant to highlight that not all macrophages, including brain microglia and Langerhans cells, arise from monocytes.

Macrophages' primary job is to ingest foreign substances that enter the body. These consist of bacteria and other particles. By digesting trash from tissues, they also get rid of apoptotic cells and recycle nutrients. Therefore, macrophages are crucial for tissue homeostasis, development, and immunity in addition to immunity. Normally dormant, these cells may become awakened during an immunological response by a number of triggers. Although the initial antigen stimulus may come through phagocytosis, helper T cell-secreted cytokines can also stimulate macrophage activity. Interferon gamma (IFN-) is one of the most effective macrophage activators. These multifarious cells can also engage in chemotaxis, which is the process of being drawn to and moved away from specific molecules. In addition to phagocytosis, macrophages are crucial in inflammation. Considering that macrophages are some of the first cells to come into contact with these intruders, they start the immune response against germs. Their toll-like and scavenger receptors, which have broad ligand specificity for proteins, oligonucleotides, polysaccharides, lectins, lipoproteins, and other compounds, are partly to blame for this [2].

In addition to carrying out these tasks, macrophages also deliver antigens to lymphocytes by expressing MHC class II molecules on their membranes. The antigens of the microorganism that the macrophages are engulfing are processed and placed on the plasmalemma's outer surface, where T helper cells will detect them. Following this recognition, T lymphocytes generate cytokines that cause B cells to become activated. Once B cells are active, they make antibodies that are tailored to the antigens the macrophage has presented. These antibodies bind to antigens on bacteria or on cells that have been infected by germs; as a result, macrophages phagocytoze these complexes with greater vigour.

Proinflammatory cytokines

Macrophages release cytokines such tumour necrosis factor (TNF), IL- 1, IL-6, IL-8, and IL-12 in response to inflammatory stimuli. These cytokines are mostly produced by monocytes and macrophages, although they are also made by activated lymphocytes, endothelial cells, and fibroblasts. In addition, leukotrienes, prostaglandins, complement, and chemokines are released by macrophages. Together, all of these chemicals have the potential to increase vascular permeability and attract inflammatory cells. These mediators not only have local effects but also systemic consequences like fever and the generation of acute inflammatory response proteins.

The 185-amino-acid glycoprotein known as tumour necrosis factor, formerly known as TNF-, was first identified for its capacity to cause tumour necrosis. It activates the immune system's acute phase of response. One of the first cytokines to be released in response to a disease, this strong pyrogenic cytokine can affect a variety of organs. TNF is one of the primary cytokines linked to septic shock as a result. TNF lowers hunger, elevates body temperature, and promotes the release of corticotropic releasing hormone in the hypothalamus [3]

Anti-Inflammatory cytokines

Numerous inhibitors and antagonists carefully control inflammation. IL-10, a 35 kD cytokine that was first discovered in 1989, is produced by T cells, B cells, and activated macrophages. Its primary functions include reducing the activation of macrophages and the generation of TNF, IL-1, IL-6, IL-8, IL-12, and GM-CSF. IL-10 is a powerful inhibitor of antigen presentation because it reduces the production of MHC-II in activated macrophages. It is particularly noteworthy that IL-10 stimulates B cell proliferation, differentiation, and IgG secretion while suppressing Th1 and NK cell production of IFN-. The effects of IL-10 on macrophages include a reduction in their ability to respond to IFN- and a reduction in their ability to kill microbes [4].

TGF- is another potent anti-inflammatory cytokine that, like IL-10, operates on a variety of target cells and reduces the inflammatory effects of TNF, IL-1, IL-2, IL-12, and other inflammatory cytokines. Although TGF- promotes Treg maintenance and activity, it also acts as a strong inhibitor of Th1 and Th2 cells.

Chemokines

Chemotaxis is the process of directing cellular movement, and chemokines are a specific class of heparin-binding cytokines that may do this. Chemokines cause cells to move in the direction of the chemokine's origin. Chemokines are essential for directing immune cells to the right locations during immunological surveillance. Some chemokines also contribute to angiogenesis or the guidance of cells to areas that offer vital signals for the differentiation of the cell during development. Chemokines are released during the inflammatory response by a wide range of cells involved in innate and adaptive immunity [5].

Acknowledgement

None.

Conflict of Interest

The author shows no conflict of interest towards this manuscript.

References

1. Sieweke, Michael H and Judith E. Allen. "Beyond stem cells: Self-renewal of differentiated macrophages." Sci 342 (2013): 1242974.

Google Scholar, Crossref, Indexed at

2. Unanue, E.R., D.I. Beller, J. Calderon, J.M. Kiely and M.J. Stadecker. "Regulation of immunity and inflammation by mediators from macrophages." Am J Pathol 85 (1976): 465.

Google Scholar, Crossref, Indexed at

3. Bernheim, Harry A and Matthew J. Kluger. "Fever and antipyresis in the lizard Dipsosaurus dorsalis." Am J Physiol Legacy Content 231 (1976): 198-203.

Google Scholar, Crossref, Indexed at

4. Stow, Jennifer L and Rachael Z. Murray. "Intracellular trafficking and secretion of inflammatory cytokines." Cytokine Growth Factor Rev 24 (2013): 227-239.

Google Scholar, Crossref, Indexed at

5. Debing, Yannick, Darius Moradpour, Johan Neyts and Jérôme Gouttenoire. "Update on hepatitis E virology: Implications for clinical practice." J Hepatol 65 (2016): 200-212.

Google Scholar, Crossref, Indexed at