Myeloid Cell Activation and Inflammatory Responses

Myeloid cells, encompassing neutrophils, monocytes and macrophages, constitute the frontline of innate immunity and orchestrate inflammatory responses to infection and tissue damage. Activation of these cells is triggered by recognition of pathogen- and damage-associated molecular patterns via cell surface receptors, leading to rapid release of pro-inflammatory cytokines, chemokines and reactive oxygen species. This initial response is essential for microbe clearance but, if unchecked, may drive tissue injury and chronic inflammation. Central to the process is a balance between activating and inhibitory signals, modulation of cell survival pathways and engagement of intracellular complexes such as inflammasomes. Recent advances have delineated molecular amplifiers of inflammation, intracellular cross-talk that limits collateral damage, and novel therapeutic approaches to recalibrate myeloid cell activation in diverse clinical settings from acute lung injury to atherosclerosis and fibrotic disease.

Research from Nature Portfolio

Studies of receptor-mediated amplification have established that blockade of a principal myeloid activation receptor reduces inflammasome-driven lung injury. In experimental models of endotoxin-induced acute lung injury, antagonism of this receptor dampens NF-κB-dependent priming of the NLRP3 inflammasome, curtails interleukin-1β release and preserves lung architecture, pointing to a precise checkpoint for therapeutic intervention. Foundational work has also revealed that receptor activation links dyslipidaemia to vascular inflammation. Under high-cholesterol conditions, upregulation of the receptor on monocytes synergises with lipid-derived factors to enhance pro-inflammatory cytokine production, monocyte expansion and foam cell formation, thereby accelerating development of atherosclerotic plaques.

Myeloid Cell Activation and Inflammatory Responses publication trend

The graph below shows the total number of articles in myeloid cell activation and inflammatory responses across all publications each year (not limited to Nature Index journals).

Technical terms

Myeloid cells: Innate immune cells including neutrophils, monocytes and macrophages that respond rapidly to infection or injury.

Triggering receptor expressed on myeloid cells-1 (TREM-1): A cell surface receptor on myeloid cells that amplifies pro-inflammatory signalling upon ligand binding.

NLRP3 inflammasome: A cytosolic multiprotein complex that activates caspase-1, leading to maturation and release of interleukin-1β and interleukin-18.

Necroptosis: A regulated form of inflammatory cell death mediated by receptor-interacting protein kinases and characterised by membrane rupture.

Soluble TREM-1 (sTREM-1): A cleaved extracellular fragment detectable in plasma that serves as a biomarker of myeloid cell activation and inflammation.

References

1. Blocking triggering receptor expressed on myeloid cells-1 attenuates lipopolysaccharide-induced acute lung injury via inhibiting NLRP3 inflammasome activation. Scientific Reports (2016).
2. TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis. Nature Communications (2016).
3. TREM1: Activation, signaling, cancer and therapy. Pharmacological Research (2024).
4. Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial. EClinicalMedicine (2023).
5. Inhibiting Triggering Receptor Expressed on Myeloid Cells-1 signaling to ameliorate skin fibrosis. JCI Insight (2024).