| First Author | Zhao XQ | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 43 | Pages | 30052-62 |
| PubMed ID | 25202022 | Mgi Jnum | J:217759 |
| Mgi Id | MGI:5615540 | Doi | 10.1074/jbc.M114.588574 |
| Citation | Zhao XQ, et al. (2014) C-type lectin receptor dectin-3 mediates trehalose 6,6'-dimycolate (TDM)-induced Mincle expression through CARD9/Bcl10/MALT1-dependent nuclear factor (NF)-kappaB activation. J Biol Chem 289(43):30052-62 |
| abstractText | Previous studies indicate that both Dectin-3 (also called MCL or Clec4d) and Mincle (also called Clec4e), two C-type lectin receptors, can recognize trehalose 6,6'-dimycolate (TDM), a cell wall component from mycobacteria, and induce potent innate immune responses. Interestingly, stimulation of Dectin-3 by TDM can also induce Mincle expression, which may enhance the host innate immune system to sense Mycobacterium infection. However, the mechanism by which Dectin-3 induces Mincle expression is not fully defined. Here, we show that TDM-induced Mincle expression is dependent on Dectin-3-mediated NF-kappaB, but not nuclear factor of activated T-cells (NFAT), activation, and Dectin-3 induces NF-kappaB activation through the CARD9-BCL10-MALT1 complex. We found that bone marrow-derived macrophages from Dectin-3-deficient mice were severely defective in the induction of Mincle expression in response to TDM stimulation. This defect is correlated with the failure of TDM-induced NF-kappaB activation in Dectin-3-deficient bone marrow-derived macrophages. Consistently, inhibition of NF-kappaB, but not NFAT, impaired TDM-induced Mincle expression, whereas NF-kappaB, but not NFAT, binds to the Mincle promoter. Dectin-3-mediated NF-kappaB activation is dependent on the CARD9-Bcl10-MALT1 complex. Finally, mice deficient for Dectin-3 or CARD9 produced much less proinflammatory cytokines and keyhole limpet hemocyanin (KLH)-specific antibodies after immunization with an adjuvant containing TDM. Overall, this study provides the mechanism by which Dectin-3 induces Mincle expression in response to Mycobacterium infection, which will have significant impact to improve adjuvant and design vaccine for antimicrobial infection. |
