The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.
Adjuvants, Immunologic
/ administration & dosage
Angiotensin-Converting Enzyme 2
/ antagonists & inhibitors
Animals
COVID-19
/ immunology
Caco-2 Cells
Cell Extracts
/ administration & dosage
Cells, Cultured
Chlorocebus aethiops
Down-Regulation
/ drug effects
Epithelial Cells
/ drug effects
HEK293 Cells
Host Microbial Interactions
/ drug effects
Humans
In Vitro Techniques
Lung
/ drug effects
Mice
Mice, Inbred BALB C
Receptors, Virus
/ antagonists & inhibitors
SARS-CoV-2
/ immunology
Serine Endopeptidases
/ drug effects
Transcription, Genetic
/ drug effects
Vero Cells
ACE2
COVID-19
OM-85
SARS-CoV-2
TMPRSS2
bacterial lysate
epithelial cells
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
11
05
2021
revised:
14
11
2021
accepted:
19
11
2021
pubmed:
14
12
2021
medline:
11
3
2022
entrez:
13
12
2021
Statut:
ppublish
Résumé
Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions. We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2. ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro. OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation. OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
Sections du résumé
BACKGROUND
Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells. OM-85, a standardized lysate of human airway bacteria with strong immunomodulating properties and an impeccable safety profile, is widely used to prevent recurrent respiratory infections. We found that airway OM-85 administration inhibits Ace2 and Tmprss2 transcription in the mouse lung, suggesting that OM-85 might hinder SARS-CoV-2/host cell interactions.
OBJECTIVES
We sought to investigate whether and how OM-85 treatment protects nonhuman primate and human epithelial cells against SARS-CoV-2.
METHODS
ACE2 and TMPRSS2 mRNA and protein expression, cell binding of SARS-CoV-2 S1 protein, cell entry of SARS-CoV-2 S protein-pseudotyped lentiviral particles, and SARS-CoV-2 cell infection were measured in kidney, lung, and intestinal epithelial cell lines, primary human bronchial epithelial cells, and ACE2-transfected HEK293T cells treated with OM-85 in vitro.
RESULTS
OM-85 significantly downregulated ACE2 and TMPRSS2 transcription and surface ACE2 protein expression in epithelial cell lines and primary bronchial epithelial cells. OM-85 also strongly inhibited SARS-CoV-2 S1 protein binding to, SARS-CoV-2 S protein-pseudotyped lentivirus entry into, and SARS-CoV-2 infection of epithelial cells. These effects of OM-85 appeared to depend on SARS-CoV-2 receptor downregulation.
CONCLUSIONS
OM-85 inhibits SARS-CoV-2 epithelial cell infection in vitro by downregulating SARS-CoV-2 receptor expression. Further studies are warranted to assess whether OM-85 may prevent and/or reduce the severity of coronavirus disease 2019.
Identifiants
pubmed: 34902435
pii: S0091-6749(21)02581-1
doi: 10.1016/j.jaci.2021.11.019
pmc: PMC8660661
pii:
doi:
Substances chimiques
Adjuvants, Immunologic
0
Broncho-Vaxom
0
Cell Extracts
0
Receptors, Virus
0
Ace2 protein, mouse
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, mouse
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
923-933.e6Subventions
Organisme : NIAID NIH HHS
ID : U19 AI125357
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007249
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI148104
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144722
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007091
Pays : United States
Organisme : NHLBI NIH HHS
ID : R25 HL126140
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.