PMID- 30941122
OWN - NLM
STAT- MEDLINE
DCOM- 20200824
LR  - 20240216
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Differential Targeting of c-Maf, Bach-1, and Elmo-1 by microRNA-143 and 
      microRNA-365 Promotes the Intracellular Growth of Mycobacterium tuberculosis in 
      Alternatively IL-4/IL-13 Activated Macrophages.
PG  - 421
LID - 10.3389/fimmu.2019.00421 [doi]
LID - 421
AB  - Mycobacterium tuberculosis (Mtb) can subvert the host defense by skewing 
      macrophage activation toward a less microbicidal alternative activated state to 
      avoid classical effector killing functions. Investigating the molecular basis of 
      this evasion mechanism could uncover potential candidates for host directed 
      therapy against tuberculosis (TB). A limited number of miRNAs have recently been 
      shown to regulate host-mycobacterial interactions. Here, we performed time course 
      kinetics experiments on bone marrow-derived macrophages (BMDMs) and human 
      monocyte-derived macrophages (MDMs) alternatively activated with IL-4, IL-13, or 
      a combination of IL-4/IL-13, followed by infection with Mtb clinical Beijing 
      strain HN878. MiR-143 and miR-365 were highly induced in Mtb-infected 
      M(IL-4/IL-13) BMDMs and MDMs. Knockdown of miR-143 and miR-365 using antagomiRs 
      decreased the intracellular growth of Mtb HN878, reduced the production of IL-6 
      and CCL5 and promoted the apoptotic death of Mtb HN878-infected M(IL-4/IL-13) 
      BMDMs. Computational target prediction identified c-Maf, Bach-1 and Elmo-1 as 
      potential targets for both miR-143 and miR-365. Functional validation using 
      luciferase assay, RNA-pulldown assay and Western blotting revealed that c-Maf and 
      Bach-1 are directly targeted by miR-143 while c-Maf, Bach-1, and Elmo-1 are 
      direct targets of miR-365. Knockdown of c-Maf using GapmeRs promoted 
      intracellular Mtb growth when compared to control treated M(IL-4/IL-13) 
      macrophages. Meanwhile, the blocking of Bach-1 had no effect and blocking Elmo-1 
      resulted in decreased Mtb growth. Combination treatment of M(IL-4/IL-13) 
      macrophages with miR-143 mimics or miR-365 mimics and c-Maf, Bach-1, or Elmo-1 
      gene-specific GapmeRs restored Mtb growth in miR-143 mimic-treated groups and 
      enhanced Mtb growth in miR-365 mimics-treated groups, thus suggesting the Mtb 
      growth-promoting activities of miR-143 and miR-365 are mediated at least 
      partially through interaction with c-Maf, Bach-1, and Elmo-1. We further show 
      that knockdown of miR-143 and miR-365 in M(IL-4/IL-13) BMDMs decreased the 
      expression of HO-1 and IL-10 which are known targets of Bach-1 and c-Maf, 
      respectively, with Mtb growth-promoting activities in macrophages. Altogether, 
      our work reports a host detrimental role of miR-143 and miR-365 during Mtb 
      infection and highlights for the first time the role and miRNA-mediated 
      regulation of c-Maf, Bach-1, and Elmo-1 in Mtb-infected M(IL-4/IL-13) 
      macrophages.
FAU - Tamgue, Ousman
AU  - Tamgue O
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
AD  - Department of Biochemistry, Faculty of Sciences, University of Douala, Douala, 
      Cameroon.
FAU - Gcanga, Lorna
AU  - Gcanga L
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
FAU - Ozturk, Mumin
AU  - Ozturk M
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
FAU - Whitehead, Lauren
AU  - Whitehead L
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
FAU - Pillay, Shandre
AU  - Pillay S
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
FAU - Jacobs, Raygaana
AU  - Jacobs R
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
FAU - Roy, Sugata
AU  - Roy S
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FAU - Schmeier, Sebastian
AU  - Schmeier S
AD  - Institute of Natural and Mathematical Sciences, Massey University, Auckland, New 
      Zealand.
FAU - Davids, Malika
AU  - Davids M
AD  - Centre for Lung Infection and Immunity, Department of Medicine and UCT Lung 
      Institute, Division of Pulmonology, University of Cape Town, Cape Town, South 
      Africa.
FAU - Medvedeva, Yulia A
AU  - Medvedeva YA
AD  - Research Center of Biotechnology, Institute of Bioengineering, Russian Academy of 
      Science, Moscow, Russia.
AD  - Department of Computational Biology, Vavilov Institute of General Genetics, 
      Russian Academy of Science, Moscow, Russia.
AD  - Department of Biological and Medical Physics, Moscow Institute of Physics and 
      Technology, Dolgoprudny, Russia.
FAU - Dheda, Keertan
AU  - Dheda K
AD  - Centre for Lung Infection and Immunity, Department of Medicine and UCT Lung 
      Institute, Division of Pulmonology, University of Cape Town, Cape Town, South 
      Africa.
AD  - Faculty of Infectious and Tropical Diseases, Department of Immunology and 
      Infection, London School of Hygiene and Tropical Medicine, London, United 
      Kingdom.
FAU - Suzuki, Harukazu
AU  - Suzuki H
AD  - RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
FAU - Brombacher, Frank
AU  - Brombacher F
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
AD  - Faculty of Health Sciences, Wellcome Centre for Infectious Diseases Research in 
      Africa, Institute of Infectious Disease and Molecular Medicine, University of 
      Cape Town, Cape Town, South Africa.
FAU - Guler, Reto
AU  - Guler R
AD  - International Centre for Genetic Engineering and Biotechnology, Cape Town 
      Component, Cape Town, South Africa.
AD  - Division of Immunology and South African Medical Research Council Immunology of 
      Infectious Diseases, Department of Pathology, Faculty of Health Sciences, 
      Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, 
      Cape Town, South Africa.
AD  - Faculty of Health Sciences, Wellcome Centre for Infectious Diseases Research in 
      Africa, Institute of Infectious Disease and Molecular Medicine, University of 
      Cape Town, Cape Town, South Africa.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190319
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Bach1 protein, mouse)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (ELMO1 protein, mouse)
RN  - 0 (Interleukin-13)
RN  - 0 (MIRN365 microRNA, mouse)
RN  - 0 (Maf protein, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN143 microRNA, mouse)
RN  - 0 (Proto-Oncogene Proteins c-maf)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*immunology
MH  - Animals
MH  - Basic-Leucine Zipper Transcription Factors/*immunology
MH  - Interleukin-13/pharmacology
MH  - Interleukin-4/pharmacology
MH  - Macrophages/drug effects/immunology/*microbiology
MH  - Male
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*immunology
MH  - Mycobacterium tuberculosis/*growth & development
MH  - Proto-Oncogene Proteins c-maf/*immunology
MH  - Tuberculosis/genetics/immunology/microbiology
PMC - PMC6433885
OTO - NOTNLM
OT  - Bach-1
OT  - CAGE transcriptomics
OT  - Elmo-1
OT  - Mycobacterium tuberculosis
OT  - alternative activated macrophages
OT  - c-Maf
OT  - microRNA-143
OT  - microRNA-365
EDAT- 2019/04/04 06:00
MHDA- 2020/08/25 06:00
PMCR- 2019/01/01
CRDT- 2019/04/04 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/04/04 06:00 [entrez]
PHST- 2019/04/04 06:00 [pubmed]
PHST- 2020/08/25 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00421 [doi]
PST - epublish
SO  - Front Immunol. 2019 Mar 19;10:421. doi: 10.3389/fimmu.2019.00421. eCollection 
      2019.