Neutrophil sub-types in maintaining immune homeostasis during steady state, infections and sterile inflammation

Abstract

Introduction Neutrophils are component of innate immune system and a) eliminate pathogens b) maintain immune homeostasis by regulating other immune cells and c) contribute to the resolution of inflammation. Neutrophil mediated inflammation has been described in pathogenesis of various diseases. This indicates neutrophils do not represent homogeneous population but perform multiple functions through confined subsets. Hence, in the present review we summarize various studies describing the heterogeneous nature of neutrophils and associated functions during steady state and pathological conditions. Methodology We performed extensive literature review with key words ‘Neutrophil subpopulations’ ‘Neutrophil subsets’, Neutrophil and infections’, ‘Neutrophil and metabolic disorders’, ‘Neutrophil heterogeneity’ in PUBMED. Results Neutrophil subtypes are characterized based on buoyancy, cell surface markers, localization and maturity. Recent advances in high throughput technologies indicate the existence of functionally diverse subsets of neutrophils in bone marrow, blood and tissues in both steady state and pathological conditions. Further, we found proportions of these subsets significantly vary in pathological conditions. Interestingly, stimulus specific activation of signalling pathways in neutrophils have been demonstrated. Conclusion Neutrophil sub-populations differ among diseases and hence, mechanisms regulating formation, sustenance, proportions and functions of these sub-types vary between physiological and pathological conditions. Hence, mechanistic insights of neutrophil subsets in disease specific manner may facilitate development of neutrophil-targeted therapies.

Exploring the Immune Response against RSV and SARS-CoV-2 Infection in Children

“…Neutrophils play a crucial role in the immune response against bacterial infections through phagocytosis and the release of antimicrobial substances. Neutrophil subpopulations vary in their capacity to initiate antimicrobial responses, encompassing actions like neutrophil extracellular trap formation, degranulation, and the synthesis of cytokines and chemokines [ 56 ]. Nevertheless, their role in viral infections is complex.…”

“…RIG-I and MDA5 are cytoplasmic viral RNA sensor proteins, comprising domains, N-terminal caspase activation and recruitment domains (CARDs), RNA helicase, and a C-terminal (CTD). RIG-I recognizes 5′ tri- or diphosphate double-stranded RNA (dsRNA) and prefers relatively short dsRNA, whereas MDA5 binds longer dsRNA [ 56 ]. RIG-I and MDA5 use the MAVS adaptor to activate TBK1, which phosphorylates IRF3, inducing type I IFN gene transcription [ 58 ].…”