| First Author | Zheng R | Year | 2018 |
| Journal | J Infect Dis | Volume | 218 |
| Issue | 2 | Pages | 312-323 |
| PubMed ID | 29228365 | Mgi Jnum | J:281773 |
| Mgi Id | MGI:6381137 | Doi | 10.1093/infdis/jix636 |
| Citation | Zheng R, et al. (2018) Notch4 Negatively Regulates the Inflammatory Response to Mycobacterium tuberculosis Infection by Inhibiting TAK1 Activation. J Infect Dis 218(2):312-323 |
| abstractText | Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of tuberculosis is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in M. tuberculosis infection remains unclear. In this study, we found that Notch4-de fi cient mice were more resistant to M. tuberculosis infection, with a much lower bacterial burden and fewer pathological changes in the lungs. Notch4 inhibited M. tuberculosis-induced production of proinflammatory cytokines by interaction with TAK1 and inhibition of its activation. Furthermore, we found that Notch intracellular domain 4 prevented TRAF6 autoubiquitination and suppressed TRAF6-mediated TAK1 polyubiquitination. Finally, Notch inhibitors made mice more resistant to M. tuberculosis infection. These results suggest that Notch4 is a negative regulator of M. tuberculosis-induced inflammatory response, and treatment with a Notch inhibitor could serve as a new therapeutic strategy for tuberculosis. |
