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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536391/ https://www.ncbi.nlm.nih.gov/pubmed/28723951 http://dx.doi.org/10.1371/journal.pntd.0005763 |
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author | Xu, Guang Mendell, Nicole L. Liang, Yuejin Shelite, Thomas R. Goez-Rivillas, Yenny Soong, Lynn Bouyer, Donald H. Walker, David H. |
author_facet | Xu, Guang Mendell, Nicole L. Liang, Yuejin Shelite, Thomas R. Goez-Rivillas, Yenny Soong, Lynn Bouyer, Donald H. Walker, David H. |
author_sort | Xu, Guang |
collection | PubMed |
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 T(reg) 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. |
format | Online Article Text |
id | pubmed-5536391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55363912017-08-07 CD8(+) T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection Xu, Guang Mendell, Nicole L. Liang, Yuejin Shelite, Thomas R. Goez-Rivillas, Yenny Soong, Lynn Bouyer, Donald H. Walker, David H. PLoS Negl Trop Dis Research Article 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 T(reg) 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. Public Library of Science 2017-07-19 /pmc/articles/PMC5536391/ /pubmed/28723951 http://dx.doi.org/10.1371/journal.pntd.0005763 Text en © 2017 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Xu, Guang Mendell, Nicole L. Liang, Yuejin Shelite, Thomas R. Goez-Rivillas, Yenny Soong, Lynn Bouyer, Donald H. Walker, David H. CD8(+) T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536391/ https://www.ncbi.nlm.nih.gov/pubmed/28723951 http://dx.doi.org/10.1371/journal.pntd.0005763 |
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