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Alveolar macrophage innate response to Mycobacterium immunogenum, the etiological agent of hypersensitivity pneumonitis: role of JNK and p38 MAPK pathways.

Authors
Chandra-H; Yadav-E; Yadav-JS
Source
PLoS One 2013 Dec; 8(12):e83172
NIOSHTIC No.
20044646
Abstract
Mycobacterium immunogenum is an emerging pathogen of the immune-mediated lung disease hypersensitivity pneumonitis (HP) reported in machinists occupationally exposed to contaminated metal working fluid (MWF). However, the mechanism of its interaction with the host lung is unclear. Considering that alveolar macrophages play a central role in host defense in the exposed lung, understanding their interaction with the pathogen could provide initial insights into the underlying immunopathogenesis events and mechanisms. In the current study, M. immunogenum 700506, a predominant genotype isolated from HP-linked fluids, was shown to multiply intracellularly, induce proinflammatory mediators (TNF-alpha, IL- 1alpha, IL-1beta, IL-6, GM-CSF, NO) and cause cytotoxicity/cell death in the cultured murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner. The responses were detected as early as 3h post-infection. Comparison of this and four additional genotypes of M. immunogenum (MJY-3, MJY-4, MJY-12, MJY-14) using an effective dose-time combination (100 MOI for 24h) showed these macrophage responses in the following order (albeit with some variations for individual response indicators). Inflammatory: MJY-3 >/= 700506 > MJY-4 >/= MJY-14 >/= MJY-12; Cytotoxic: 700506 >/= MJY-3 > MJY-4 >/= MJY-12 >/= MJY-14. In general, 700506 and MJY-3 showed a more aggressive response than other genotypes. Chemical blocking of either p38 or JNK inhibited the induction of proinflammatory mediators (cytokines, NO) by 700506. However, the cellular responses showed a somewhat opposite effect. This is the first report on M. immunogenum interactions with alveolar macrophages and on the identification of JNK- and p38- mediated signaling and its role in mediating the proinflammatory responses during these interactions.
Keywords
Respiratory-hypersensitivity; Alveolar-cells; Bacteria; Microorganisms; Pathology; Immune-reaction; Immune-system; Lung-disease; Hypersensitivity; Immunotoxins; Cell-damage; Cellular-reactions; Cytotoxic-effects; Dose-response; Machinists; Metalworking-fluids; Etiology
Contact
Jagjit S. Yadav, Microbial Pathogenesis Laboratory, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056 USA
CODEN
POLNCL
Publication Date
20131211
Document Type
Journal Article
Email Address
jagjit.yadav@uc.edu
Funding Type
Grant
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-007364
Issue of Publication
12
ISSN
1932-6203
Source Name
Public Library of Science One
State
OH
Performing Organization
University of Cincinnati
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