Organic Dust Exposure Enhances SARS-CoV-2 Entry in a PKCa- and ADAM-17-Dependent Manner

Details

• Personal Author:
  Bauer CD ; Muralidharan A ; Nissen CG ; Poole JA ; Reid SP ; Wyatt TA
• Description:
  SARS-CoV-2, the causative agent of the COVID-19 pandemic, has had a global impact, affecting millions over the last three years. Pre-existing lung diseases adversely affect the prognosis of infected COVID-19 patients, and agricultural workers routinely exposed to inhalable organic dusts have substantial increased risk for developing chronic lung diseases. In previous studies, we characterized the protein kinase C (PKC)-dependent airway inflammation mediated by organic dust extract (ODE) derived from dust collected from swine confinement facilities in in vitro and in vivo models. Here, we studied the effect of ODE on SARS-CoV-2 pseudoviral infection in mice and human bronchial epithelial cells (BEAS-2B). In wild-type (WT) and transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor (SARS-CoV-2 entry receptor), ODE increased ACE2 shedding by ADAM-17 in the lungs. After repeated ODE treatments, the increased soluble ACE2 correlated to higher pseudovirus titer in the mouse lungs. In the human bronchial epithelial cells, ODE augmented PKCa activity in WT cells, and membrane ACE2 expression was diminished in PKCa-dominant negative cells. Unlike in the mice, increasing membrane ACE2 levels by treating with PKCa or ADAM-17 inhibitors and a low dose of ODE enhanced pseudoviral entry in vitro. Following viral entry, IL-8 secretion by the cells was diminished in a PKCa- and ADAM-17-independent manner. Together, the complex mechanisms involved in the synergistic effects of agricultural dust and SARS-CoV-2 highlight the importance of studying dust-mediated changes to immunity against circulating pathogens. [Description provided by NIOSH]
• Subjects:
  Communicable Diseases Dust Immune System Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  ACE2 ADAM-17 Author Keywords: SARS-CoV-2 Bioaerosols COVID-19 Immune Reaction Inhalation Lung Disease ODE Organic Dust Organic Dusts Pathogens PKCa SARS-CoV-2

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• ISSN:
  2673-8937
• Document Type:
  Text
• Funding:
  Grant ; Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  486-497
• Volume:
  4
• Issue:
  3
• NIOSHTIC Number:
  nn:20070557
• Citation:
  Int J Transl Med 2024 Sep; 4(3):486-497
• Contact Point Address:
  Todd A. Wyatt, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
• Email:
  twyatt@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20210901
• Source Full Name:
  International Journal of Translational Medicine
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:fecb6a86274382ba5bca65b35c35d4a8d37f2aeac1574938104ebe7d004243588905ae22e8741a5c0888797e3f25da23a8bf685f8f41b43d5f57c14133311ee8
• Download URL:
  https://stacks.cdc.gov/view/cdc/208741/cdc_208741_DS1.pdf
• File Type:
  [PDF - 3.43 MB ]