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

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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.

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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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Authors and Affiliations

  1. Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Daejeon, 301-747, South Korea

    Hye-Mi Lee, Jae-Min Yuk, Dong-Min Shin & Eun-Kyeong Jo

  2. Infection Signaling Network Research Center, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Daejeon, 301-747, South Korea

    Hye-Mi Lee, Jae-Min Yuk, Dong-Min Shin & Eun-Kyeong Jo

  3. Research Institute for Medical Sciences, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Daejeon, 301-747, South Korea

    Eun-Kyeong Jo

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  1. Hye-Mi Lee
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Correspondence to Eun-Kyeong Jo.

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Lee, HM., Yuk, JM., Shin, DM. et al. Dectin-1 is Inducible and Plays an Essential Role for Mycobacteria-Induced Innate Immune Responses in Airway Epithelial Cells. J Clin Immunol 29, 795–805 (2009). https://doi.org/10.1007/s10875-009-9319-3

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  • DOI: https://doi.org/10.1007/s10875-009-9319-3

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