Abstract
The evolution of macrophages has made them primordial for both development and immunity. Their functions range from the shaping of body plans to the ingestion and elimination of apoptotic cells and pathogens. Cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. A portfolio of cytokines is central to the role of macrophages as sentries of the innate immune system that mediate the transition from innate to adaptive immunity. In concert with other mediators, cytokines bias the fate of macrophages into a spectrum of inflammation-promoting “classically activated,” to anti-inflammatory or “alternatively activated” macrophages. Deregulated cytokine secretion is implicated in several disease states ranging from chronic inflammation to allergy. Macrophages release cytokines via a series of beautifully orchestrated pathways that are spatiotemporally regulated. At the molecular level, these exocytic cytokine secretion pathways are coordinated by multi-protein complexes that guide cytokines from their point of synthesis to their ports of exit into the extracellular milieu. These trafficking proteins, many of which were discovered in yeast and commemorated in the 2013 Nobel Prize in Physiology or Medicine, coordinate the organelle fusion steps that are responsible for cytokine release. This review discusses the functions of cytokines secreted by macrophages, and summarizes what is known about their release mechanisms. This information will be used to delve into how selected pathogens subvert cytokine release for their own survival.
Highlights
CYTOKINES AND MACROPHAGES Macrophages are phagocytic cells of the innate immune system that are located in various tissues
Most macrophages are derived from bone marrow precursor cells that develop into monocytes
These are formed in the bone marrow from stem cells of the granulocytic–monocytic lineage that are exposed to cytokines such as the granulocyte macrophage colony stimulating factor (GMCSF) and interleukin-3 (IL-3)
Summary
CYTOKINES AND MACROPHAGES Macrophages are phagocytic cells of the innate immune system that are located in various tissues. The Russian scientist Elie Metchnikoff received the 1908 Nobel Prize in Physiology or Medicine for his work on immunity when he observed that when he punctured starfish larvae, a population of cells migrated to the wound He observed cells that were able to uptake particles that had been placed in the digestive tracts of the larvae. After 1969, the concept of the mononuclear phagocyte system – formed by a variety of macrophages derived from monocytes from the bone marrow – was introduced to replace the concept of the reticuloendothelial system, which is constituted of functionally and immunologically distinct cells. Albeit phagocytosis may provide the initial antigen stimulus, the activity of macrophages can be increased by cytokines secreted by helper T cells, with interferon gamma (IFN-γ) being one of the most potent macrophage activators These multifaceted cells are capable of chemotaxis, www.frontiersin.org
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