Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis.
MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interpl...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4529177?pdf=render |
| _version_ | 1819138278898532352 |
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| author | Robert B Lochhead James F Zachary Luciana Dalla Rosa Ying Ma John H Weis Ryan M O'Connell Janis J Weis |
| author_facet | Robert B Lochhead James F Zachary Luciana Dalla Rosa Ying Ma John H Weis Ryan M O'Connell Janis J Weis |
| author_sort | Robert B Lochhead |
| collection | DOAJ |
| description | MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity. |
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| id | doaj.art-e5ea112f0ccb4c0fae54a3c86d09dce9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T11:04:14Z |
| publishDate | 2015-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-e5ea112f0ccb4c0fae54a3c86d09dce92022-12-21T18:28:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013514210.1371/journal.pone.0135142Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis.Robert B LochheadJames F ZacharyLuciana Dalla RosaYing MaJohn H WeisRyan M O'ConnellJanis J WeisMicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity.http://europepmc.org/articles/PMC4529177?pdf=render |
| spellingShingle | Robert B Lochhead James F Zachary Luciana Dalla Rosa Ying Ma John H Weis Ryan M O'Connell Janis J Weis Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. PLoS ONE |
| title | Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. |
| title_full | Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. |
| title_fullStr | Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. |
| title_full_unstemmed | Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. |
| title_short | Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis. |
| title_sort | antagonistic interplay between microrna 155 and il 10 during lyme carditis and arthritis |
| url | http://europepmc.org/articles/PMC4529177?pdf=render |
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