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Title: Early immunopathological events in acute model of mycobacterial hypersensitivity pneumonitis in mice.

Authors: Johansson, Elisabet; Boivin, Gregory P; Yadav, Jagjit S

Published In J Immunotoxicol, (2017 Dec)

Abstract: 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- (TNFα, IL-6, IL-1β) 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)-γ, 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.

PubMed ID: 28094581 Exiting the NIEHS site

MeSH Terms: Acute Disease; Alveolitis, Extrinsic Allergic/epidemiology; Alveolitis, Extrinsic Allergic/immunology*; Animals; Antigens, Bacterial/immunology; Cytokines/metabolism; Disease Models, Animal; Genotype; Humans; Lung/immunology*; Lung/microbiology; Male; Metallurgy; Mice; Mice, Inbred C57BL; Mycobacterium Infections/epidemiology; Mycobacterium Infections/immunology*; Mycobacterium/genetics; Mycobacterium/immunology*; Mycobacterium/pathogenicity; Occupational Exposure/statistics & numerical data; Risk; Virulence

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Last Reviewed: October 02, 2024