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| Status |
Public on Jun 01, 2021 |
| Title |
Impact of Wnt6 knockout in Mtb infected murine BMDM |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
In view of emerging drug-resistant tuberculosis, host directed therapies are urgently needed to improve treatment outcomes with currently available anti-tuberculosis therapies. One option is to interfere with the formation of lipid-laden “foamy” macrophages in the infected host. Here, we provide evidence that WNT6, a member of the evolutionary conserved WNT signaling pathway, promotes foam cell formation by regulating key lipid metabolic genes including acetyl-CoA carboxylase-2 (ACC2) during pulmonary TB. In addition, we demonstrate that Mycobacterium tuberculosis (Mtb) facilitates its intracellular growth and dissemination in the host by exploiting the WNT6-ACC2 pathway. Using genetic and pharmacological approaches, we show that lack of functional WNT6 or ACC2 significantly reduces intracellular TAG levels, Mtb growth and necrotic cell death of macrophages. In combination with the anti-TB drug isoniazid, pharmacological inhibition of ACC2 improved anti-mycobacterial treatment in vitro and in vivo. Therefore, we propose the WNT6-ACC2 signaling pathway as a promising target for a host-directed therapy to reduce intracellular replication of Mtb by modulating neutral lipid metabolism.
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| Overall design |
3 wildtype vs 3 knockout mice
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| |
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| Contributor(s) |
Brandenburg J, Reiling N, Marwitz S |
| Citation(s) |
34255743 |
| |
| Submission date |
Oct 25, 2020 |
| Last update date |
Sep 01, 2021 |
| Contact name |
Sebastian Marwitz |
| Organization name |
Research Center Borstel - Leibniz Lung Center
|
| Department |
Histology
|
| Street address |
Parkallee 3a
|
| City |
Borstel |
| ZIP/Postal code |
23845 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA671683 |
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