Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

Abstract

Neutrophils are the most abundant circulating and first-responding innate myeloid cells and have so far been underestimated in the context of multiple sclerosis (MS). MS is the most frequent, immune-mediated, inflammatory disease of the central nervous system. MS is treatable but not curable and its cause(s) and pathogenesis remain elusive. The involvement of neutrophils in MS pathogenesis has been suggested by the use of preclinical animal disease models, as well as on the basis of patient sample analysis. In this review, we provide an overview of the possible mechanisms and functions by which neutrophils may contribute to the development and pathology of MS. Neutrophils display a broad variety of effector functions enabling disease pathogenesis, including (1) the release of inflammatory mediators and enzymes, such as interleukin-1β, myeloperoxidase and various proteinases, (2) destruction and phagocytosis of myelin (as debris), (3) release of neutrophil extracellular traps, (4) production of reactive oxygen species, (5) breakdown of the blood–brain barrier and (6) generation and presentation of autoantigens. An important question relates to the issue of whether neutrophils exhibit a predominantly proinflammatory function or are also implicated in the resolution of chronic inflammatory responses in MS.

Peripheral Immune Cell Ratios and Clinical Outcomes in Seropositive Autoimmune Encephalitis: A Study by the Australian Autoimmune Encephalitis Consortium

“…The exact pathophysiological mechanism that underpins the relationship between NLR and first line treatment failure in this study is unclear. Neutrophils are an essential part of the early inflammatory cascade, and contribute to breakdown of the blood-brain barrier ( 24 , 25 ). We hypothesize that dysregulated innate immune activation, increased circulating neutrophils and sequestration of lymphocytes are indicative of a heightened inflammatory response.…”

Neutrophil‐to‐lymphocyte ratio and CRP as biomarkers in multiple sclerosis: A systematic review

“…10 Accordingly, CRP serves as a biomarker of disease activity in other immune-mediated disorders such as Crohn's disease 11 and rheumatoid arthritis. 12 The differential count of white blood cells is widely used as a marker of systemic inflammation and infection, and a recent review article suggested that neutrophils and their phenotypes potentially can be linked to specific disease courses of MS. 13 However, NLR seems to better reflect systemic inflammation compared with the specific counts for neutrophils and lymphocytes alone. NLR is calculated as the ratio of neutrophil-to-lymphocyte count, which makes it a simple, rapid, non-specific, and inexpensive way of detecting increased systemic inflammation.…”

Prevention of EAE by PEGylated Antigenic Peptides

“…Although the influx of inflammatory cells was not completely prevented by vaccination with pMOG-PEG20, total hematopoietic cells were significantly reduced to approximately 1/3. Notably macrophages and neutrophils that have both been implicated in pathology of MS (Mishra and Yong, 2016; De Bondt et al, 2020) were strongly reduced. This underlines the protective effects of pMOG-PEG20 vaccination recorded in the clinical symptoms.…”