Survival of COVID-19 patients requires precise immune regulation: The hypothetical immunoprotective role of nicotinic agonists

Receptors of innate immune cells function synergistically to detect pathogens and elicit appropriate immune responses. Many receptor pairs also appear “colocalized” on the membranes of phagosomes, the intracellular compartments for pathogen ingestion. However, the nature of the seemingly receptor colocalization and the role it plays in immune regulation are unclear, due to the inaccessibility of intracellular phagocytic receptors. Here, we report a geometric manipulation technique to directly probe the role of phagocytic receptor “colocalization” in innate immune regulation. Using particles with spatially patterned ligands as phagocytic targets, we can decouple the receptor pair, Dectin-1 and Toll-like receptor (TLR)2, to opposite sides on a single phagosome or bring them into nanoscale proximity without changing the overall membrane composition. We show that Dectin-1 enhances immune responses triggered predominantly by TLR2 when their centroid-to-centroid proximity is <500 nm, but this signaling synergy diminishes upon receptor segregation beyond this threshold distance. Our results demonstrate that nanoscale proximity, not necessarily colocalization, between Dectin-1 and TLR2 is required for their synergistic regulation of macrophage immune responses. This study elucidates the relationship between the spatial organization of phagocytic receptors and innate immune responses. It showcases a technique that allows spatial manipulation of receptors and their signal cross-talk on phagosomes inside living cells.

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Neutrophils in liver diseases: pathogenesis and therapeutic targets

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00560-0 ◽

2020 ◽

Vol 18 (1) ◽

pp. 38-44 ◽

Cited By ~ 1

Author(s):

Kai Liu ◽

Fu-Sheng Wang ◽

Ruonan Xu

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Cancer ◽

Immune Regulation ◽

Liver Diseases ◽

Immune Modulation ◽

Functional Plasticity ◽

Homogeneous Population ◽

Patients With Cancer

AbstractPreviously, it was assumed that peripheral neutrophils are a homogeneous population that displays antimicrobial functions. However, recent data have revealed that neutrophils are heterogeneous and are additionally involved in tissue damage and immune regulation. The phenotypic and functional plasticity of neutrophils has been identified in patients with cancer, inflammatory disorders, infections, and other diseases. Currently, neutrophils, with their autocrine, paracrine, and immune modulation functions, have been shown to be involved in liver diseases, including viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, liver fibrosis, cirrhosis, liver failure, and liver cancer. Accordingly, this review summarizes the role of neutrophils in liver diseases.

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