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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Research

MyD88 regulates a prolonged adaptation response to environmental dust exposure-induced lung disease

Authors: Amber N. Johnson, Jack R. Harkema, Amy J. Nelson, John D. Dickinson, Julianna Kalil, Michael J. Duryee, Geoffrey M. Thiele, Balawant Kumar, Amar B. Singh, Rohit Gaurav, Sarah C. Glover, Ying Tang, Debra J. Romberger, Tammy Kielian, Jill A. Poole

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Environmental organic dust exposures enriched in Toll-like receptor (TLR) agonists can reduce allergic asthma development but are associated with occupational asthma and chronic bronchitis. The TLR adaptor protein myeloid differentiation factor88 (MyD88) is fundamental in regulating acute inflammatory responses to organic dust extract (ODE), yet its role in repetitive exposures is unknown and could inform future strategies.

Methods

Wild-type (WT) and MyD88 knockout (KO) mice were exposed intranasally to ODE or saline daily for 3 weeks (repetitive exposure). Repetitively exposed animals were also subsequently rested with no treatments for 4 weeks followed by single rechallenge with saline/ODE.

Results

Repetitive ODE exposure induced neutrophil influx and release of pro-inflammatory cytokines and chemokines were profoundly reduced in MyD88 KO mice. In comparison, ODE-induced cellular aggregates, B cells, mast cell infiltrates and serum IgE levels remained elevated in KO mice and mucous cell metaplasia was increased. Expression of ODE-induced tight junction protein(s) was also MyD88-dependent. Following recovery and then rechallenge with ODE, inflammatory mediators, but not neutrophil influx, was reduced in WT mice pretreated with ODE coincident with increased expression of IL-33 and IL-10, suggesting an adaptation response. Repetitively exposed MyD88 KO mice lacked inflammatory responsiveness upon ODE rechallenge.

Conclusions

MyD88 is essential in mediating the classic airway inflammatory response to repetitive ODE, but targeting MyD88 does not reduce mucous cell metaplasia, lymphocyte influx, or IgE responsiveness. TLR-enriched dust exposures induce a prolonged adaptation response that is largely MyD88-independent. These findings demonstrate the complex role of MyD88-dependent signaling during acute vs. chronic organic dust exposures.
Appendix
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Metadata
Title
MyD88 regulates a prolonged adaptation response to environmental dust exposure-induced lung disease
Authors
Amber N. Johnson
Jack R. Harkema
Amy J. Nelson
John D. Dickinson
Julianna Kalil
Michael J. Duryee
Geoffrey M. Thiele
Balawant Kumar
Amar B. Singh
Rohit Gaurav
Sarah C. Glover
Ying Tang
Debra J. Romberger
Tammy Kielian
Jill A. Poole
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01362-8

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