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


CONCLUSIONS
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.
Lee
Hye-Mi
HM
Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea.
Yuk
Jae-Min
JM
Shin
Dong-Min
DM
Jo
Eun-Kyeong
EK
D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics*; D009161:Mycobacterium / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger; D012137:Respiratory System / Q000166:cytology* / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism; D000099181:Dectin-1
D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019061:src-Family Kinases; D000099181:Dectin-1