Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria

Am J Respir Cell Mol Biol. 2018 Feb;58(2):241-252. doi: 10.1165/rcmb.2017-0218OC.

Abstract

The incidence of pulmonary nontuberculous mycobacteria (NTM) disease is increasing, but host responses in respiratory epithelium infected with NTM are not fully understood. In this work, we aimed to identify infection-relevant gene expression signatures of NTM infection of the respiratory epithelium. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium subsp. avium (MAC) or Mycobacterium abscessus subsp. abscessus (MAB). We used cells from four different donors to obtain generalizable data. Differentiated respiratory epithelial cells at the ALI were infected with MAC or MAB at a multiplicity of infection of 100:1 or 1,000:1, and RNA sequencing was performed at Days 1 and 3 after infection. In response to infection, we found down-regulation of ciliary genes but upregulation of genes associated with cytokines/chemokines, such as IL-32, and cholesterol biosynthesis. Inflammatory response genes tended to be more upregulated by MAB than by MAC infection. Primary respiratory epithelial cell infection with NTM at the ALI identified ciliary function, cholesterol biosynthesis, and cytokine/chemokine production as major host responses to infection. Some of these pathways may be amenable to therapeutic manipulation.

Keywords: RNA-seq; air–liquid interface method; pulmonary nontuberculous mycobacteria disease.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Bacterial Adhesion / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Cholesterol / biosynthesis*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • Female
  • Gene Expression Profiling
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Interleukins / biosynthesis
  • Interleukins / immunology
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / genetics
  • Mycobacterium Infections, Nontuberculous / immunology*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Nontuberculous Mycobacteria / immunology*
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / microbiology

Substances

  • IL17A protein, human
  • IL32 protein, human
  • Interleukin-17
  • Interleukins
  • Cholesterol