Dectin-1 is inducible and plays an essential role for mycobacteria-induced innate immune responses in airway epithelial cells

J Clin Immunol. 2009 Nov;29(6):795-805. doi: 10.1007/s10875-009-9319-3. Epub 2009 Jul 25.


Introduction: Airway epithelial cells are the first cells to be challenged upon contact with mycobacteria. In response, they express pattern-recognition receptors that play fundamental roles as sentinels and mediators of pulmonary innate immunity. The c-type lectin Dectin-1 is expressed predominantly on the surface of myeloid lineage cells. In this study, we examined the induction, regulation, and functions of Dectin-1 in pulmonary epithelial cells.

Results: Mycobacterium tuberculosis (Mtb) actively induced the expression of Dectin-1 mRNA and protein in A549 cells in a toll-like receptor (TLR) 2-dependent manner. In addition, Mtb-mediated generation of reactive oxygen species and Dectin-1 induction were mutually dependent. Moreover, Mtb actively induced the phosphorylation of Src family kinases at Tyr416 via TLR2. Selective inhibition of Src markedly attenuated the induction of Mtb-dependent Dectin-1 expression, indicating that Src kinases are crucial regulators of Dectin-1-dependent signaling. Mtb internalization was partially blocked by silencing Dectin-1 expression, inhibiting Src kinases, or pretreating with antioxidants. Finally, Dectin-1 was required for pro-inflammatory cytokine release and antimicrobial effects on intracellular mycobacterial growth in A549 cells.

Conclusion: Collectively, our findings demonstrate the novel induction of Dectin-1 in type II airway epithelial cells and its critical role in the innate immune response against Mtb in non-phagocytic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Epithelial Cells / immunology*
  • Humans
  • Immunity, Innate*
  • Lectins, C-Type
  • Membrane Proteins / genetics*
  • Mycobacterium / immunology*
  • Nerve Tissue Proteins / genetics*
  • Phosphorylation
  • RNA, Messenger
  • Respiratory System / cytology*
  • Respiratory System / immunology
  • Transcriptional Activation / immunology
  • src-Family Kinases / metabolism


  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • dectin 1
  • src-Family Kinases