Induction of a cytokine storm involves suppression of the Osteopontin-dependent TH1 response.

Autor: Fnu G; University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA., Hudock K; Division of Pulmonary, Critical Care & Sleep Medicine, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA.; Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Powers-Fletcher M; Infectious Diseases Division, Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA., Huang RP; RayBiotech, Peachtree Corners, Georgia, USA., Weber GF; University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2022 Oct; Vol. 167 (2), pp. 165-180. Date of Electronic Publication: 2022 Aug 10.
DOI: 10.1111/imm.13524
Abstrakt: Cytokine release syndromes represent a severe turn in certain disease states, which may be caused by several infections, including those with the virus SARS-CoV-2. This inefficient, even harmful, immune response has been associated with a broad release of chemokines. Although a cellular (type I) immune reaction is efficacious against viral infections, we noted a type I deficit in the cytokine patterns produced by cytokine storms of all reported etiologies. Agents including lipopolysaccharide (LPS, bacterial), anti-CD3 (antibody) and a version of the prominent SARS-CoV-2 viral surface molecule, Spike Glycoprotein, were individually sufficient to induce IL-6 and multiple chemokines in mice. They failed to upregulate the TH1 inducer cytokine Osteopontin, and the pathophysiologic triggers actually suppressed the PMA-induced Osteopontin secretion from monocytic cells. Osteopontin administration partially reversed the chemokine elevation, more effectively so in a mouse strain with TH1 bias. Corroboration was obtained from the inverse correlation in the levels of IL-6 and Osteopontin in plasma samples from acute COVID-19 patients. We hypothesize that the inhibition of Osteopontin by SARS-CoV-2 Spike Glycoprotein or LPS represents an immune evasion mechanism employed by the pathogens of origin. The ensuing dysfunctional inflammatory response promotes a vicious cycle of amplification, resulting in a cytokine storm.
(© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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