Monocytes, a special type of white blood cell, secrete cytokines as inflammatory messengers that are crucial for an adequate immune response. Monocytes are white blood cells, also known as leukocytes. They are an important part of the innate immune system and contribute to host defense in the blood by secreting large amounts of proinflammatory cytokines. Abnormal monocyte activity leads to hyperinflammation, i.e. very severe inflammation, as well as life-threatening cytokine storms. On the other hand, disturbed monocyte function is associated with “immune paralysis”. In this condition, the immune system’s ability to fight invaders such as viruses and bacteria is inhibited. This increases susceptibility to infections. Researchers from the University Hospital Bonn and the University of Bonn have now discovered that platelets, also called thrombocytes, communicate with monocytes and increase their inflammatory capacity.
By understanding the platelet-monocyte interaction, they hope to improve the treatment of immune disorders and associated diseases. Platelets play a central role in blood clotting, but are also believed to play important roles in the immune system. Prof. Franklin’s research group has already identified platelets as an important regulator of inflammation. They now report that a low platelet count in the rare blood disease immune thrombocytopenia (ITP) or the artificial removal of platelets from healthy monocytes causes “immunoparalysis”. This is characterized by a disturbed cytokine response and is an immunological challenge. Surprisingly, supplementing the monocytes with fresh platelets reverses this condition and restores the monocyte cytokine response. Researchers have discovered that platelets serve as reservoirs of key cytokine transcription regulators, such as NF-κB, and have identified enrichment of the platelet transcription factor NF-κB2 in human monocytes using proteomics.
Platelets proportionally restore impaired cytokine production in human monocytes lacking MAPK p38α, NF-κB p65, and NF-κB2. The study findings suggest a novel mechanism of intercellular communication in which platelets regulate monocyte function. Platelets, in simple terms, are a source of microscopic vesicles like “exosomes” that carry numerous protein messages that can coordinate with the main immunological signals. This is demonstrated by the fact that the number of platelets directly affects the production of cytokines by CD14+ monocytes towards the stimulation of the Toll-like receptor (TLR) and the Nod-like receptor (NLR), which are sensors of pathogenic substances or corpuscles. However, in human monocytes, they found that the removal of platelets further modulated the activity of the AIM2 and NLRC4 inflammasomes that, unlike NLRP3, do not require a trigger by the bacterial endotoxin LPS.
In support of this conclusion, the removal of platelets affected the monocyte production of inflammasome-independent IL-6 and TNFα after LPS priming. As they squeeze, platelets release microvesicles that are rich in some transcription factors that monocytes lack, prompting them to synthesize cytokines and other immune regulators when needed. Already in 2020, the team of professor Franklin proved that plateles boost the inflammasome capacity of human macrophages and neutrophils, that are critical for IL-1 production by monocytes in malaria: they license NLRP3 transcription for the subsequent IL-1 secretion. This effect was revelaed to be indipendent of cell-to-cell contact, platelet-derived lipid mediators, purines, nucleic acids or platelet cytokines, and it involves the triggering of calcium-sensing receptors on macrophages. The scientists say that clinically, this suggests potential therapeutic strategies to counteract monocyte immune paralysis, and they hope that understanding platelet-monocyte interactions could lead to better treatment of platelet-related immune disorders and othe immune diseases.
- Edited by Dr. Gianfrancesco Cormaci, PhD, Specialist in Clinical Biochemistry.
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