PMID- 37590294
OWN - NLM
STAT- MEDLINE
DCOM- 20230912
LR  - 20230930
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 21
IP  - 8
DP  - 2023 Aug
TI  - NCoR1 controls Mycobacterium tuberculosis growth in myeloid cells by regulating 
      the AMPK-mTOR-TFEB axis.
PG  - e3002231
LID - 10.1371/journal.pbio.3002231 [doi]
LID - e3002231
AB  - Mycobacterium tuberculosis (Mtb) defends host-mediated killing by repressing the 
      autophagolysosome machinery. For the first time, we report NCoR1 co-repressor as 
      a crucial host factor, controlling Mtb growth in myeloid cells by regulating both 
      autophagosome maturation and lysosome biogenesis. We found that the dynamic 
      expression of NCoR1 is compromised in human peripheral blood mononuclear cells 
      (PBMCs) during active Mtb infection, which is rescued upon prolonged 
      anti-mycobacterial therapy. In addition, a loss of function in myeloid-specific 
      NCoR1 considerably exacerbates the growth of M. tuberculosis in vitro in THP1 
      differentiated macrophages, ex vivo in bone marrow-derived macrophages (BMDMs), 
      and in vivo in NCoR1MyeKO mice. We showed that NCoR1 depletion controls the 
      AMPK-mTOR-TFEB signalling axis by fine-tuning cellular adenosine triphosphate 
      (ATP) homeostasis, which in turn changes the expression of proteins involved in 
      autophagy and lysosomal biogenesis. Moreover, we also showed that the treatment 
      of NCoR1 depleted cells by Rapamycin, Antimycin-A, or Metformin rescued the TFEB 
      activity and LC3 levels, resulting in enhanced Mtb clearance. Similarly, 
      expressing NCoR1 exogenously rescued the AMPK-mTOR-TFEB signalling axis and Mtb 
      killing. Overall, our data revealed a central role of NCoR1 in Mtb pathogenesis 
      in myeloid cells.
CI  - Copyright: (c) 2023 Biswas et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Biswas, Viplov Kumar
AU  - Biswas VK
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Sen, Kaushik
AU  - Sen K
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - Regional Centre for Biotechnology, Faridabad, India.
FAU - Ahad, Abdul
AU  - Ahad A
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
FAU - Ghosh, Arup
AU  - Ghosh A
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Verma, Surbhi
AU  - Verma S
AD  - Molecular Medicine: Cellular Immunology, International Centre for Genetic 
      Engineering and Biotechnology (ICGEB), New Delhi, India.
FAU - Pati, Rashmirekha
AU  - Pati R
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
FAU - Prusty, Subhasish
AU  - Prusty S
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - Regional Centre for Biotechnology, Faridabad, India.
FAU - Nayak, Sourya Prakash
AU  - Nayak SP
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
FAU - Podder, Sreeparna
AU  - Podder S
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Kumar, Dhiraj
AU  - Kumar D
AD  - Molecular Medicine: Cellular Immunology, International Centre for Genetic 
      Engineering and Biotechnology (ICGEB), New Delhi, India.
FAU - Gupta, Bhawna
AU  - Gupta B
AD  - School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
FAU - Raghav, Sunil Kumar
AU  - Raghav SK
AUID- ORCID: 0000-0001-9913-4241
AD  - Immuno-genomics & Systems Biology Laboratory, Institute of Life Sciences (ILS), 
      Bhubaneswar, India.
AD  - School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), 
      Bhubaneswar, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230817
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (TFEB protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (NCOR1 protein, human)
RN  - 0 (Nuclear Receptor Co-Repressor 1)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - AMP-Activated Protein Kinases
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
MH  - Leukocytes, Mononuclear
MH  - *Mycobacterium tuberculosis
MH  - Myeloid Cells
MH  - TOR Serine-Threonine Kinases
MH  - *Nuclear Receptor Co-Repressor 1/metabolism
PMC - PMC10465006
COIS- The authors have declared that no competing interests exist
EDAT- 2023/08/17 18:42
MHDA- 2023/08/31 06:41
PMCR- 2023/08/17
CRDT- 2023/08/17 13:45
PHST- 2022/10/18 00:00 [received]
PHST- 2023/07/04 00:00 [accepted]
PHST- 2023/08/29 00:00 [revised]
PHST- 2023/08/31 06:41 [medline]
PHST- 2023/08/17 18:42 [pubmed]
PHST- 2023/08/17 13:45 [entrez]
PHST- 2023/08/17 00:00 [pmc-release]
AID - PBIOLOGY-D-22-02314 [pii]
AID - 10.1371/journal.pbio.3002231 [doi]
PST - epublish
SO  - PLoS Biol. 2023 Aug 17;21(8):e3002231. doi: 10.1371/journal.pbio.3002231. 
      eCollection 2023 Aug.