Early Immunopathological Events in Acute Model of Mycobacterial Hypersensitivity Pneumonitis in Mice

Details

• Personal Author:
  Boivin GP ; Johansson E ; Yadav JS
• Description:
  Prolonged exposure to antigens of non-tuberculous mycobacteria species colonizing industrial metalworking fluid (MWF), particularly Mycobacterium immunogenum (MI), has been implicated in chronic forms of hypersensitivity pneumonitis (HP) in machinists based on epidemiology studies and long-term exposure of mouse models. However, a role of short-term acute exposure to these antigens has not been described in the context of acute forms of HP. This study investigated short-term acute exposure of mice to MI cell lysate (or live cell suspension) via oropharyngeal aspiration. The results showed there was a dose- and time-dependent increase (peaking at 2 h post-instillation) in lung immunological responses in terms of the pro- (TNFa, IL-6, IL-1b) and anti-inflammatory (IL-10) cytokines. Bronchoalveolar lavage and histology showed neutrophils as the predominant infiltrating cell type, with lymphocytes <5% at all timepoints or concentrations. Granulomatous inflammation peaked between 8 and 24 h post-exposure, and resolved by 96 h. Live bacterial challenge, typically encountered in real-world exposures, showed no significant differences from bacterial lysate except for induction of appreciable levels of interferon (IFN)-gamma, implying additional immunogenic potential. Collectively, the short-term mycobacterial challenge in mice led to a transient early immunopathologic response, with little adaptive immunity, which is consistent with events associated with human acute forms of HP. Screening of MWF-originated mycobacterial genotypes/variants (six of MI, four of M. chelonae, two of M. abscessus) showed both inter- and intra-species differences, with MI genotype MJY10 being the most immunogenic. In conclusion, this study characterized the first short-term mycobacterial exposure mouse model that mimics acute HP in machinists; this could serve as a potentially useful model for rapid screening of field MWF-associated mycobacteria for routine and timely occupational risk assessment and for investigating early biomarkers and mechanisms of this understudied immune lung disease. [Description provided by NIOSH]
• Subjects:
  Alveolitis, Extrinsic Allergic Animals Antigens Immune System Lung Diseases Manufacturing And Industrial Facilities Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Acute Exposure Animal Studies Author Keywords: Mycobacterium Immunogenum Bronchoalveolar Lavage Cytokines Exposure Assessment Hypersensitivity Pneumonitis Immune Reaction Immunopathological Changes Inhalation Lung Disease Lung Pathology Machine Operators Machinists Metalworking Fluid Metalworking Fluids Models Mouse MWFs Mycobacterium

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• ISSN:
  1547-691X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  77-88
• Volume:
  14
• Issue:
  1
• NIOSHTIC Number:
  nn:20052369
• Citation:
  J Immunotoxicol 2017 Jan; 14(1):77-88
• Contact Point Address:
  Jagjit S. Yadav, Ph.D, Department of Environmental Health, University of Cincinnati College of Medicine, Kettering Laboratory Complex, 160 Panzeca Way, Cincinnati, OH 45267-0056, USA
• Email:
  jagjit.yadav@uc.edu
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20170731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5dbbe982e1052ae81696df6b693b7acd54aebcb6faeed6326a05958d3a8ad3d2c7e572e5f619d4e36734660d503de65e9c924a1427bbf8f72e1194f9168de98b
• Download URL:
  https://stacks.cdc.gov/view/cdc/211905/cdc_211905_DS1.pdf
• File Type:
  [PDF - 2.19 MB ]