Perforin, COVID-19 and a possible pathogenic auto-inflammatory feedback loop.
Animals
Autoimmunity
/ genetics
COVID-19
/ epidemiology
Cytokine Release Syndrome
/ epidemiology
Disease Resistance
Humans
Interleukin-6
/ metabolism
Killer Cells, Natural
/ immunology
Lymphohistiocytosis, Hemophagocytic
/ epidemiology
Neutrophils
/ immunology
Perforin
/ genetics
SARS-CoV-2
/ physiology
COVID
auto‐inflammatory
cytokine storm
haemophagocytic lymphohistiocytosis
interleukin‐6
natural killer cell
perforin
Journal
Scandinavian journal of immunology
ISSN: 1365-3083
Titre abrégé: Scand J Immunol
Pays: England
ID NLM: 0323767
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
revised:
31
08
2021
received:
01
07
2021
accepted:
07
09
2021
entrez:
10
11
2021
pubmed:
11
11
2021
medline:
16
11
2021
Statut:
ppublish
Résumé
During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy.
Identifiants
pubmed: 34755902
doi: 10.1111/sji.13102
pmc: PMC8646999
doi:
Substances chimiques
Interleukin-6
0
Perforin
126465-35-8
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13102Subventions
Organisme : Medical Research Council
ID : MR/V006746/1
Pays : United Kingdom
Informations de copyright
© 2021 The Scandinavian Foundation for Immunology.
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