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Series GSE160039 Query DataSets for GSE160039
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.
 
Overall design 3 wildtype vs 3 knockout mice
 
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 Pathology
Street address Parkallee 3a
City Borstel
ZIP/Postal code 23845
Country Germany
 
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (6)
GSM4855813 Wt_infected_Rep1
GSM4855814 Wnt6_Ko_infected_Rep1
GSM4855815 Wt_infected_Rep2
Relations
BioProject PRJNA671683

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE160039_RAW.tar 53.5 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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