Myd88 controls airway epithelial Muc5ac expression during TLR activation conditions from agricultural organic dust exposure

John D. Dickinson, Jenea M. Sweeter, Elizabeth B. Staab, Amy J. Nelson, Kristina L. Bailey, Kristi J. Warren, Ana Maria Jaramillo, Burton F. Dickey, Jill A. Poole

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Inflammation from airborne microbes can overwhelm compensatory mucociliary clearance mechanisms, leading to mucous cell metaplasia. Toll-like receptor (TLR) activation via myeloid differentiation factor 88 (MyD88) signaling is central to pathogen responses. We have previously shown that agricultural organic dust extract (ODE), with abundant microbial component diversity, activates TLR-induced airway inflammation. With the use of an established model, C57BL/6J wild-type (WT) and global MyD88 knockout (KO) mice were treated with intranasal inhalation of ODE or saline, daily for 1 wk. ODE primarily increased mucin (Muc)5ac levels relative to Muc5b. Compared with ODE-challenged WT mice, ODE-challenged, MyD88-deficient mice demonstrated significantly increased Muc5ac immunostaining, protein levels by immunoblot, and expression by quantitative PCR. The enhanced Muc5ac levels in MyD88-deficient mice were not explained by differences in the differentiation program of airway secretory cells in naïve mice. Increased Muc5ac levels in MyD88-deficient mice were also not explained by augmented inflammation, IL-17A, or neutrophil elastase levels. Furthermore, the enhanced airway mucins in the MyD88-deficient mice were not due to defective secretion, as the mucin secretory capacity of MyD88-KO mice remained intact. Finally, ODE-induced Muc5ac levels were enhanced in MyD88-deficient airway epithelial cells in vitro. In conclusion, MyD88 deficiency enhances airway mucous cell metaplasia under environments with high TLR activation.

Original languageEnglish (US)
Pages (from-to)L334-L347
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume316
Issue number2
DOIs
StatePublished - Feb 2019

Keywords

  • Agriculture
  • Airway
  • Epithelial
  • Lung
  • Muc5ac
  • Muc5b
  • Mucin
  • MyD88
  • Organic dust

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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