Neutralization of IL-33 Modifies the Type 2 and Type 3 Inflammatory Signature of Viral Induced Asthma Exacerbation

Details

• Personal Author:
  DeVasure JM ; Dickinson JD ; Peebles RS Jr. ; Poole JA ; Sweeter JM ; Warren KJ ; Wyatt TA ; DeVasure JM ; Dickinson JD ; Peebles RS Jr. ; Poole JA ; Sweeter JM ; Warren KJ ; Wyatt TA
• Description:
  Background: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVAtreated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Asthma, Occupational Laboratories Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety Viral Diseases
• Keywords:
  Airway Obstruction Author Keywords: Interleukin-33 Bronchial Asthma Group 2 Innate Lymphoid Cells Group 3 Innate Lymphoid Cells IL-23 IL-33 ILC2 ILC3 Interleukin-23 Laboratory Animals Lung Function Proteins Respiratory Infections Respiratory Syncytial Virus-A2 Respiratory System Disorders RSV-A2 Thymic Stromal Lymphopoietin TSLP Viral Infections

  More +
• ISSN:
  1465-9921
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 4 ; OSHA Region 7 ; OSHA Region 8 ; Tennessee ; Utah
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  22
• NIOSHTIC Number:
  nn:20063099
• Citation:
  Respir Res 2021 Jul; 22:206
• Contact Point Address:
  Kristi J. Warren, Division of Pulmonary Medicine, Department of Internal Medicine, University of Utah Health, 26 N 1900 E, Salt Lake City, UT 84132
• Email:
  kristi.warren@hsc.utah.edu
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Agriculture, Forestry and Fishing ; Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Respiratory Research
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5ae18ab81fd6487a4316bd494c28f977a32d885d0be8cde8c4f6422a9b4d0a7797bd840999db8b68529c4ae1d51aaba51e9d94a07a0138953c4911aaee2f4140
• Download URL:
  https://stacks.cdc.gov/view/cdc/226222/cdc_226222_DS1.pdf
• File Type:
  [PDF - 3.42 MB ]