CD82 hypomethylation is essential for tuberculosis pathogenesis via regulation of RUNX1-Rab5/22

Experimental & Molecular Medicine
Hyun-Jung KohChul-Su Yang

Abstract

The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression. Targeting of the runt-related transcription factor 1 (RUNX1) by CD82 is essential for phagosome arrest via interacting with Rab5/22. This arrest is required for the intracellular growth of MTB in vitro and in vivo, but not for that of MTB H37Ra (MTB Ra) in macrophages. In addition, knockdown or knockout of CD82 or RUNX1 increased antibacterial host defense via phagolysosome biogenesis, inflammatory cytokine production, and subsequent antimicrobial activity both in vitro and in vivo. Notably, the levels of CD82 and RUNX1 in granulomas were elevated in tuberculosis (TB) patients, indicating that CD82 and RUNX1 have clinical significance in human TB. Our findings identify a previously unrecognized r...Continue Reading

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Citations

Aug 14, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nida S KhanJatin M Vyas
Sep 10, 2020·Cellular Microbiology·Jona KaramWassim Daher

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Methods Mentioned

BETA
PCR
genotyping
transfections
immunoprecipitation
pulldown
RNA-seq
ELISA
GTPase
co-immunoprecipitation
transfection

Software Mentioned

STAR
DESeq2
MethPrimer
ToolGen
GraphPad Prism
HOMER
SPSS
Trimmomatic

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