Experimental Model of Pulmonary Inflammation Induced by SARS-CoV-2 Spike Protein and Endotoxin

Overview

Journal ACS Pharmacol Transl Sci

Publisher American Chemical Society

Specialty Biochemistry

Date 2022 Jul 1

PMID 35774232

Authors

Manoj Puthia

Lloyd Tanner

Ganna Petruk

Artur Schmidtchen

Affiliations

Soon will be listed here.

Abstract

COVID-19 is characterized by a dysregulated and excessive inflammatory response and, in severe cases, acute respiratory distress syndrome. We have recently demonstrated a previously unknown high-affinity interaction between the SARS-CoV-2 spike (S) protein and bacterial lipopolysaccharide (LPS), leading to the boosting of inflammation. Here we present a mouse inflammation model employing the coadministration of aerosolized S protein together with LPS to the lungs. Using NF-κB-RE-Luc reporter and C57BL/6 mice followed by combinations of bioimaging, cytokine, chemokine, fluorescence-activated cell sorting, and histochemistry analyses, we show that the model yields severe pulmonary inflammation and a cytokine profile similar to that observed in COVID-19. Therefore, the model offers utility for analyses of the pathophysiological features of COVID-19 and the development of new treatments.

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References

Munoz-Fontela C, Dowling W, Funnell S, Gsell P, Riveros-Balta A, Albrecht R . Animal models for COVID-19. Nature. 2020; 586(7830):509-515. PMC: 8136862. DOI: 10.1038/s41586-020-2787-6. View

Rubin E, Longo D, Baden L . Interleukin-6 Receptor Inhibition in Covid-19 - Cooling the Inflammatory Soup. N Engl J Med. 2021; 384(16):1564-1565. PMC: 7944949. DOI: 10.1056/NEJMe2103108. View

Alqahtani J, Oyelade T, Aldhahir A, Alghamdi S, Almehmadi M, Alqahtani A . Prevalence, Severity and Mortality associated with COPD and Smoking in patients with COVID-19: A Rapid Systematic Review and Meta-Analysis. PLoS One. 2020; 15(5):e0233147. PMC: 7213702. DOI: 10.1371/journal.pone.0233147. View

Puthia M, Butrym M, Petrlova J, Stromdahl A, Andersson M, Kjellstrom S . A dual-action peptide-containing hydrogel targets wound infection and inflammation. Sci Transl Med. 2020; 12(524). DOI: 10.1126/scitranslmed.aax6601. View

Parolin C, Virtuoso S, Giovanetti M, Angeletti S, Ciccozzi M, Borsetti A . Animal Hosts and Experimental Models of SARS-CoV-2 Infection. Chemotherapy. 2021; 66(1-2):8-16. PMC: 8089426. DOI: 10.1159/000515341. View

Felsenstein S, Herbert J, McNamara P, Hedrich C . COVID-19: Immunology and treatment options. Clin Immunol. 2020; 215:108448. PMC: 7185015. DOI: 10.1016/j.clim.2020.108448. View

Dinnon 3rd K, Leist S, Schafer A, Edwards C, Martinez D, Montgomery S . A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures. Nature. 2020; 586(7830):560-566. PMC: 8034761. DOI: 10.1038/s41586-020-2708-8. View

Zhou Z, Ren L, Zhang L, Zhong J, Xiao Y, Jia Z . Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients. Cell Host Microbe. 2020; 27(6):883-890.e2. PMC: 7196896. DOI: 10.1016/j.chom.2020.04.017. View

Jarnagin K, Alvarez O, Shresta S, Webb D . Animal models for SARS-Cov2/Covid19 research-A commentary. Biochem Pharmacol. 2021; 188:114543. PMC: 8016548. DOI: 10.1016/j.bcp.2021.114543. View

10.

Johansen M, Irving A, Montagutelli X, Tate M, Rudloff I, Nold M . Animal and translational models of SARS-CoV-2 infection and COVID-19. Mucosal Immunol. 2020; 13(6):877-891. PMC: 7439637. DOI: 10.1038/s41385-020-00340-z. View

11.

Tay M, Poh C, Renia L, Macary P, Ng L . The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20(6):363-374. PMC: 7187672. DOI: 10.1038/s41577-020-0311-8. View

12.

Stromdahl A, Ignatowicz L, Petruk G, Butrym M, Wasserstrom S, Schmidtchen A . Peptide-coated polyurethane material reduces wound infection and inflammation. Acta Biomater. 2021; 128:314-331. DOI: 10.1016/j.actbio.2021.04.045. View

13.

Matute-Bello G, Downey G, Moore B, Groshong S, Matthay M, Slutsky A . An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011; 44(5):725-38. PMC: 7328339. DOI: 10.1165/rcmb.2009-0210ST. View

14.

Szabo P, Dogra P, Gray J, Wells S, Connors T, Weisberg S . Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19. Immunity. 2021; 54(4):797-814.e6. PMC: 7951561. DOI: 10.1016/j.immuni.2021.03.005. View

15.

Lakdawala S, Menachery V . The search for a COVID-19 animal model. Science. 2020; 368(6494):942-943. DOI: 10.1126/science.abc6141. View

16.

Jones S, Hunter C . Is IL-6 a key cytokine target for therapy in COVID-19?. Nat Rev Immunol. 2021; 21(6):337-339. PMC: 8043092. DOI: 10.1038/s41577-021-00553-8. View

17.

Saravanan R, Holdbrook D, Petrlova J, Singh S, Berglund N, Choong Y . Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides. Nat Commun. 2018; 9(1):2762. PMC: 6050251. DOI: 10.1038/s41467-018-05242-0. View

18.

Petrlova J, Petruk G, Huber R, McBurnie E, van der Plas M, Bond P . Thrombin-derived C-terminal fragments aggregate and scavenge bacteria and their proinflammatory products. J Biol Chem. 2020; 295(11):3417-3430. PMC: 7076200. DOI: 10.1074/jbc.RA120.012741. View

19.

Osuchowski M, Winkler M, Skirecki T, Cajander S, Shankar-Hari M, Lachmann G . The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity. Lancet Respir Med. 2021; 9(6):622-642. PMC: 8102044. DOI: 10.1016/S2213-2600(21)00218-6. View

20.

Carsana L, Sonzogni A, Nasr A, Rossi R, Pellegrinelli A, Zerbi P . Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis. 2020; 20(10):1135-1140. PMC: 7279758. DOI: 10.1016/S1473-3099(20)30434-5. View