@article{Tamgue2019,
abstract = {Mycobacterium tuberculosis (Mtb) can subvert the host defence by skewing macrophage activation towards 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.},
author = {Tamgue, Ousman and Gcanga, Lorna and Ozturk, Mumin and Whitehead, Lauren and Pillay, Shandre and Jacobs, Raygaana and Roy, Sugata and Schmeier, Sebastian and Davids, Malika and Medvedeva, Yulia A and Dheda, Keertan and Suzuki, Harukazu and Brombacher, Frank and Guler, Reto},
doi = {10.3389/fimmu.2019.00421},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tamgue et al. - 2019 - Differential targeting of c-Maf, Bach-1, and Elmo-1 by microRNA-143 and microRNA-365 promotes the intracellular g.pdf:pdf},
journal = {Frontiers in Immunology},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {mar},
pages = {421},
pmid = {30941122},
publisher = {Frontiers},
title = {{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}},
url = {https://www.frontiersin.org/article/10.3389/fimmu.2019.00421/full},
volume = {10},
year = {2019}
}

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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.","author":[{"propositions":[],"lastnames":["Tamgue"],"firstnames":["Ousman"],"suffixes":[]},{"propositions":[],"lastnames":["Gcanga"],"firstnames":["Lorna"],"suffixes":[]},{"propositions":[],"lastnames":["Ozturk"],"firstnames":["Mumin"],"suffixes":[]},{"propositions":[],"lastnames":["Whitehead"],"firstnames":["Lauren"],"suffixes":[]},{"propositions":[],"lastnames":["Pillay"],"firstnames":["Shandre"],"suffixes":[]},{"propositions":[],"lastnames":["Jacobs"],"firstnames":["Raygaana"],"suffixes":[]},{"propositions":[],"lastnames":["Roy"],"firstnames":["Sugata"],"suffixes":[]},{"propositions":[],"lastnames":["Schmeier"],"firstnames":["Sebastian"],"suffixes":[]},{"propositions":[],"lastnames":["Davids"],"firstnames":["Malika"],"suffixes":[]},{"propositions":[],"lastnames":["Medvedeva"],"firstnames":["Yulia","A"],"suffixes":[]},{"propositions":[],"lastnames":["Dheda"],"firstnames":["Keertan"],"suffixes":[]},{"propositions":[],"lastnames":["Suzuki"],"firstnames":["Harukazu"],"suffixes":[]},{"propositions":[],"lastnames":["Brombacher"],"firstnames":["Frank"],"suffixes":[]},{"propositions":[],"lastnames":["Guler"],"firstnames":["Reto"],"suffixes":[]}],"doi":"10.3389/fimmu.2019.00421","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Tamgue et al. - 2019 - Differential targeting of c-Maf, Bach-1, and Elmo-1 by microRNA-143 and microRNA-365 promotes the intracellular g.pdf:pdf","journal":"Frontiers in Immunology","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"mar","pages":"421","pmid":"30941122","publisher":"Frontiers","title":"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","url":"https://www.frontiersin.org/article/10.3389/fimmu.2019.00421/full","volume":"10","year":"2019","bibtex":"@article{Tamgue2019,\r\nabstract = {Mycobacterium tuberculosis (Mtb) can subvert the host defence by skewing macrophage activation towards a less microbicidal alternative activated state to avoid classical effector killing functions. 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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. 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