Dectin-1 is Inducible and Plays an Essential Role for Mycobacteria-Induced Innate Immune Responses in Airway Epithelial Cells

  • Hye-Mi Lee
  • Jae-Min Yuk
  • Dong-Min Shin
  • Eun-Kyeong Jo
Article
First Online:
Received:
Accepted:

Abstract

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.

Keywords

Mycobacterium tuberculosis epithelial cells reactive oxygen species Src innate immune responses 
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Notes

Acknowledgements

This work was supported by a grant of the Korea Science and Engineering Foundation through the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University. We thank Dr. R. L. Friedman for Mtb H37Rv; Dr. S. G. Franzbalu for Mtb-GFP; Dr. K. Kwon for bacterial strains; and Dr. C. V. Harding for 19-kDa antigen. The authors have no financial conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Hye-Mi Lee
    • 1
    • 2
  • Jae-Min Yuk
    • 1
    • 2
  • Dong-Min Shin
    • 1
    • 2
  • Eun-Kyeong Jo
    • 1
    • 2
    • 3
  1. 1.Department of Microbiology, College of MedicineChungnam National UniversityDaejeonSouth Korea
  2. 2.Infection Signaling Network Research Center, College of MedicineChungnam National UniversityDaejeonSouth Korea
  3. 3.Research Institute for Medical Sciences, College of MedicineChungnam National UniversityDaejeonSouth Korea

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