Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.
Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known a...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4718649?pdf=render |
| _version_ | 1819225767144325120 |
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| author | Masashi Matsuyama Yukio Ishii Hirofumi Sakurai Satoshi Ano Yuko Morishima Keigyou Yoh Satoru Takahashi Kenji Ogawa Nobuyuki Hizawa |
| author_facet | Masashi Matsuyama Yukio Ishii Hirofumi Sakurai Satoshi Ano Yuko Morishima Keigyou Yoh Satoru Takahashi Kenji Ogawa Nobuyuki Hizawa |
| author_sort | Masashi Matsuyama |
| collection | DOAJ |
| description | Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection. |
| first_indexed | 2024-12-23T10:14:49Z |
| format | Article |
| id | doaj.art-69c031b5c0154e908a751e9f82a1f8b9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T10:14:49Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-69c031b5c0154e908a751e9f82a1f8b92022-12-21T17:50:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014706410.1371/journal.pone.0147064Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.Masashi MatsuyamaYukio IshiiHirofumi SakuraiSatoshi AnoYuko MorishimaKeigyou YohSatoru TakahashiKenji OgawaNobuyuki HizawaMycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection.http://europepmc.org/articles/PMC4718649?pdf=render |
| spellingShingle | Masashi Matsuyama Yukio Ishii Hirofumi Sakurai Satoshi Ano Yuko Morishima Keigyou Yoh Satoru Takahashi Kenji Ogawa Nobuyuki Hizawa Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. PLoS ONE |
| title | Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. |
| title_full | Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. |
| title_fullStr | Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. |
| title_full_unstemmed | Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. |
| title_short | Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium. |
| title_sort | overexpression of rorγt enhances pulmonary inflammation after infection with mycobacterium avium |
| url | http://europepmc.org/articles/PMC4718649?pdf=render |
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