Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner
As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockou...
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| Veröffentlicht in: | International immunopharmacology 2019-08, Vol.73, p.41-48 |
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| creator | Wu, Haichong Bao, Yanqing Wang, Lin Li, Xiujun Sun, Jianjun |
| description | As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockout strain Mm∆EsxA/B, recombinant EsxA, EsxB and EsxA/B heterodimer proteins, we provide evidence that down-regulation of miR-148ais dependent on EsxA, and up-regulation of miR-148a reduces Mm intracellular survival. Moreover, up-regulation of miR-148a down-regulates the pro-inflammatory cytokines (e.g. TNF-α and IL-1β) and the TLR4-mediated NF-κB activation. Together, miR-148a may function as an anti-inflammation modulator in responses to mycobacterial infection. Regulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.
•miR-148a plays an important role in mycobacterial infection of macrophages.•miR-148a is downregulated in a EsxA-dependent manner, and upregulation of miR-148a reduces Mm intracellular survival.•TLR4 expression and NF-κB activation were both inhibited by miR-148a treatment.•Upregulation of miR-148a may provide a novel venue in development of therapies in tuberculosis. |
| doi_str_mv | 10.1016/j.intimp.2019.04.056 |
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•miR-148a plays an important role in mycobacterial infection of macrophages.•miR-148a is downregulated in a EsxA-dependent manner, and upregulation of miR-148a reduces Mm intracellular survival.•TLR4 expression and NF-κB activation were both inhibited by miR-148a treatment.•Upregulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2019.04.056</identifier><identifier>PMID: 31078924</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bacterial Proteins - genetics ; Cytokines ; Down-Regulation ; ESAT-6 ; EsxA ; IL-1β ; Immune response ; Inflammation ; Interleukin-1beta - genetics ; Interleukin-1beta - metabolism ; Macrophages ; Mice ; MicroRNAs ; miR-148a ; Mycobacterium marinum ; Mycobacterium marinum - genetics ; Mycobacterium tuberculosis ; NF-kappa B - metabolism ; NF-κB protein ; RAW 264.7 Cells ; TLR4 protein ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Tuberculosis ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Virulence ; Virulence factors</subject><ispartof>International immunopharmacology, 2019-08, Vol.73, p.41-48</ispartof><rights>2019 Elsevier B.V.</rights><rights>Copyright © 2019 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Aug 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-f1d12bbefbf863e44fe742fa729e09cb8bcccf031d9517fc836d320a0925f4c23</citedby><cites>FETCH-LOGICAL-c491t-f1d12bbefbf863e44fe742fa729e09cb8bcccf031d9517fc836d320a0925f4c23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576919304138$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31078924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Haichong</creatorcontrib><creatorcontrib>Bao, Yanqing</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Li, Xiujun</creatorcontrib><creatorcontrib>Sun, Jianjun</creatorcontrib><title>Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockout strain Mm∆EsxA/B, recombinant EsxA, EsxB and EsxA/B heterodimer proteins, we provide evidence that down-regulation of miR-148ais dependent on EsxA, and up-regulation of miR-148a reduces Mm intracellular survival. Moreover, up-regulation of miR-148a down-regulates the pro-inflammatory cytokines (e.g. TNF-α and IL-1β) and the TLR4-mediated NF-κB activation. Together, miR-148a may function as an anti-inflammation modulator in responses to mycobacterial infection. Regulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.
•miR-148a plays an important role in mycobacterial infection of macrophages.•miR-148a is downregulated in a EsxA-dependent manner, and upregulation of miR-148a reduces Mm intracellular survival.•TLR4 expression and NF-κB activation were both inhibited by miR-148a treatment.•Upregulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.</description><subject>Animals</subject><subject>Bacterial Proteins - genetics</subject><subject>Cytokines</subject><subject>Down-Regulation</subject><subject>ESAT-6</subject><subject>EsxA</subject><subject>IL-1β</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Interleukin-1beta - genetics</subject><subject>Interleukin-1beta - metabolism</subject><subject>Macrophages</subject><subject>Mice</subject><subject>MicroRNAs</subject><subject>miR-148a</subject><subject>Mycobacterium marinum</subject><subject>Mycobacterium marinum - genetics</subject><subject>Mycobacterium tuberculosis</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>RAW 264.7 Cells</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Tuberculosis</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu1TAQtRCIPuAPELoSGzYJHsexnQ1SVZWCVISEQGJnOfb41leJE-ykpX-Pr24pjwWrefjM8Zw5hLwAWgMF8WZXh7iEca4Zha6mvKateESOQUlVgaTt45K3QlatFN0ROcl5R2npc3hKjhqgUnWMH5NvH-_s1Bu7YArruBlNCrFEN93GKuF2HcyCeTOGzxVwZTYhFohN03xttqVfShM3F_nHWeVwxugwLgUQI6Zn5Ik3Q8bn9_GUfH138eX8fXX16fLD-dlVZXkHS-XBAet79L1XokHOPUrOvJGsQ9rZXvXWWk8bcF0L0lvVCNcwamjHWs8ta07J2wPvvPYjOls2SGbQcwpFy52eTNB_v8RwrbfTjRYCBAVaCF7fE6Tp-4p50WPIFofBRJzWrBlrQHHFWl6gr_6B7qY1xSKvoISU0Ci1J-QHVLlTzgn9wzJA9d46vdMH6_TeOk25LtaVsZd_CnkY-uXVb6VYznkTMOlsA0aLLiS0i3ZT-P8PPwF2Dq2c</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Wu, Haichong</creator><creator>Bao, Yanqing</creator><creator>Wang, Lin</creator><creator>Li, Xiujun</creator><creator>Sun, Jianjun</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190801</creationdate><title>Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner</title><author>Wu, Haichong ; Bao, Yanqing ; Wang, Lin ; Li, Xiujun ; Sun, Jianjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-f1d12bbefbf863e44fe742fa729e09cb8bcccf031d9517fc836d320a0925f4c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Bacterial Proteins - genetics</topic><topic>Cytokines</topic><topic>Down-Regulation</topic><topic>ESAT-6</topic><topic>EsxA</topic><topic>IL-1β</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>Interleukin-1beta - genetics</topic><topic>Interleukin-1beta - metabolism</topic><topic>Macrophages</topic><topic>Mice</topic><topic>MicroRNAs</topic><topic>miR-148a</topic><topic>Mycobacterium marinum</topic><topic>Mycobacterium marinum - genetics</topic><topic>Mycobacterium tuberculosis</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>RAW 264.7 Cells</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Tuberculosis</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Haichong</creatorcontrib><creatorcontrib>Bao, Yanqing</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Li, Xiujun</creatorcontrib><creatorcontrib>Sun, Jianjun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Haichong</au><au>Bao, Yanqing</au><au>Wang, Lin</au><au>Li, Xiujun</au><au>Sun, Jianjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2019-08-01</date><risdate>2019</risdate><volume>73</volume><spage>41</spage><epage>48</epage><pages>41-48</pages><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>As a key virulence factor of Mycobacterium tuberculosis, EsxA is not only involved in phagosome rupture, but also functions in stimulation of immune responses in macrophages. Here, we report thatmiR-148a is down-regulated in the macrophages infected with Mycobacterium marinum (Mm). Using the knockout strain Mm∆EsxA/B, recombinant EsxA, EsxB and EsxA/B heterodimer proteins, we provide evidence that down-regulation of miR-148ais dependent on EsxA, and up-regulation of miR-148a reduces Mm intracellular survival. Moreover, up-regulation of miR-148a down-regulates the pro-inflammatory cytokines (e.g. TNF-α and IL-1β) and the TLR4-mediated NF-κB activation. Together, miR-148a may function as an anti-inflammation modulator in responses to mycobacterial infection. Regulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.
•miR-148a plays an important role in mycobacterial infection of macrophages.•miR-148a is downregulated in a EsxA-dependent manner, and upregulation of miR-148a reduces Mm intracellular survival.•TLR4 expression and NF-κB activation were both inhibited by miR-148a treatment.•Upregulation of miR-148a may provide a novel venue in development of therapies in tuberculosis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31078924</pmid><doi>10.1016/j.intimp.2019.04.056</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bacterial Proteins - genetics Cytokines Down-Regulation ESAT-6 EsxA IL-1β Immune response Inflammation Interleukin-1beta - genetics Interleukin-1beta - metabolism Macrophages Mice MicroRNAs miR-148a Mycobacterium marinum Mycobacterium marinum - genetics Mycobacterium tuberculosis NF-kappa B - metabolism NF-κB protein RAW 264.7 Cells TLR4 protein Toll-Like Receptor 4 - metabolism Toll-like receptors Tuberculosis Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Virulence Virulence factors |
| title | Mycobacterium marinum down-regulates miR-148a in macrophages in an EsxA-dependent manner |
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