CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection.
Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treat...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-07-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC5536391?pdf=render |
| _version_ | 1818495122148425728 |
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| author | Guang Xu Nicole L Mendell Yuejin Liang Thomas R Shelite Yenny Goez-Rivillas Lynn Soong Donald H Bouyer David H Walker |
| author_facet | Guang Xu Nicole L Mendell Yuejin Liang Thomas R Shelite Yenny Goez-Rivillas Lynn Soong Donald H Bouyer David H Walker |
| author_sort | Guang Xu |
| collection | DOAJ |
| description | Scrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i.v.) disseminated infection mouse model, we observed that more CD8+ T cells than CD4+ T cells were present in the spleen of infected mice at 12 dpi. We also determined that Treg cells and the proportion of T cells producing IL-10 were significantly increased from 6 dpi, which correlated with the onset of illness, body weight loss, and increased bacterial loads. We further studied CD8-/-, MHC I-/- and wild type control (WT) C57BL/6J mice to determine the importance of CD8+ T cells and MHC I molecules. After infection with an ordinarily sub-lethal dose of O. tsutsugamushi, all CD8-/- and MHC I-/- mice were moribund between 12 and 15 dpi, whereas all WT mice survived. Bacterial loads in the lung, kidney, liver and spleen of CD8-/- and MHC I-/- mice were significantly greater than those in WT mice. Interferon-γ (IFN-γ) and granzyme B mRNA levels in the liver of CD8-/- and MHC I-/- mice were significantly greater than in WT mice. In addition, more severe histopathologic lesions were observed in CD8-/- mice. Finally, adoptive transfer confirmed a major role of immune CD8+ T cells as well as a less effective contribution by immune CD8 T cell-depleted splenocytes in protection against O. tsutsugamushi infection. These studies demonstrated the critical importance of CD8+ T cells in the host immune response during O. tsutsugamushi infection. |
| first_indexed | 2024-12-10T18:16:08Z |
| format | Article |
| id | doaj.art-3587c79fe0494f2a9f0b6f3b95e12a85 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-10T18:16:08Z |
| publishDate | 2017-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-3587c79fe0494f2a9f0b6f3b95e12a852022-12-22T01:38:19ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-07-01117e000576310.1371/journal.pntd.0005763CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection.Guang XuNicole L MendellYuejin LiangThomas R SheliteYenny Goez-RivillasLynn SoongDonald H BouyerDavid H WalkerScrub typhus, caused by a Gram-negative obligately intracellular coccobacillus, Orientia tsutsugamushi, is a long neglected but important tropical disease. Orientia tsutsugamushi causes illness in one million people each year, and 1 billion people are at risk. Without appropriate diagnosis and treatment, the disease can cause severe multiorgan failure with a case fatality rate of 7-15%. The current gaps in knowledge of immunity include the unknown mechanisms of host immunity to O. tsutsugamushi. Using an intravenous (i.v.) disseminated infection mouse model, we observed that more CD8+ T cells than CD4+ T cells were present in the spleen of infected mice at 12 dpi. We also determined that Treg cells and the proportion of T cells producing IL-10 were significantly increased from 6 dpi, which correlated with the onset of illness, body weight loss, and increased bacterial loads. We further studied CD8-/-, MHC I-/- and wild type control (WT) C57BL/6J mice to determine the importance of CD8+ T cells and MHC I molecules. After infection with an ordinarily sub-lethal dose of O. tsutsugamushi, all CD8-/- and MHC I-/- mice were moribund between 12 and 15 dpi, whereas all WT mice survived. Bacterial loads in the lung, kidney, liver and spleen of CD8-/- and MHC I-/- mice were significantly greater than those in WT mice. Interferon-γ (IFN-γ) and granzyme B mRNA levels in the liver of CD8-/- and MHC I-/- mice were significantly greater than in WT mice. In addition, more severe histopathologic lesions were observed in CD8-/- mice. Finally, adoptive transfer confirmed a major role of immune CD8+ T cells as well as a less effective contribution by immune CD8 T cell-depleted splenocytes in protection against O. tsutsugamushi infection. These studies demonstrated the critical importance of CD8+ T cells in the host immune response during O. tsutsugamushi infection.http://europepmc.org/articles/PMC5536391?pdf=render |
| spellingShingle | Guang Xu Nicole L Mendell Yuejin Liang Thomas R Shelite Yenny Goez-Rivillas Lynn Soong Donald H Bouyer David H Walker CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. PLoS Neglected Tropical Diseases |
| title | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. |
| title_full | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. |
| title_fullStr | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. |
| title_full_unstemmed | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. |
| title_short | CD8+ T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. |
| title_sort | cd8 t cells provide immune protection against murine disseminated endotheliotropic orientia tsutsugamushi infection |
| url | http://europepmc.org/articles/PMC5536391?pdf=render |
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