Your browser doesn't support javascript.
Perforin, COVID-19 and a possible pathogenic auto-inflammatory feedback loop.
Cunningham, Louise; Kimber, Ian; Basketter, David; Simmonds, Peter; McSweeney, Sheila; Tziotzios, Christos; McFadden, John P.
  • Cunningham L; St. John's Institute of Dermatology, Guy's and St Thomas' Hospital, London, UK.
  • Kimber I; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
  • Basketter D; DABMEB Consultancy Ltd, Wotton-under-Edge, UK.
  • Simmonds P; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • McSweeney S; St. John's Institute of Dermatology, Guy's and St Thomas' Hospital, London, UK.
  • Tziotzios C; St. John's Institute of Dermatology, Guy's and St Thomas' Hospital, London, UK.
  • McFadden JP; St. John's Institute of Dermatology, Guy's and St Thomas' Hospital, London, UK.
Scand J Immunol ; 94(5): e13102, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1434833
ABSTRACT
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Lymphohistiocytosis, Hemophagocytic / Perforin / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Observational study Limits: Animals / Humans Language: English Journal: Scand J Immunol Year: 2021 Document Type: Article Affiliation country: Sji.13102

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Lymphohistiocytosis, Hemophagocytic / Perforin / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Neutrophils Type of study: Observational study Limits: Animals / Humans Language: English Journal: Scand J Immunol Year: 2021 Document Type: Article Affiliation country: Sji.13102