CD8+T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection

Guang Xu, Nicole L. Mendell, Yuejin Liang, Thomas Shelite, Yenny Goez-Rivillas, Lynn Soong, Donald Bouyer, David Walker

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 Tregcells 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.

Original languageEnglish (US)
Article numbere0005763
JournalPLoS Neglected Tropical Diseases
Volume11
Issue number7
DOIs
StatePublished - Jul 19 2017

Fingerprint

Orientia tsutsugamushi
T-Lymphocytes
Infection
Bacterial Load
Immunity
Spleen
Scrub Typhus
Granzymes
Adoptive Transfer
Liver
Inbred C57BL Mouse
Interleukin-10
Interferons
Weight Loss
Body Weight

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

CD8+T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection. / Xu, Guang; Mendell, Nicole L.; Liang, Yuejin; Shelite, Thomas; Goez-Rivillas, Yenny; Soong, Lynn; Bouyer, Donald; Walker, David.

In: PLoS Neglected Tropical Diseases, Vol. 11, No. 7, e0005763, 19.07.2017.

Research output: Contribution to journalArticle

@article{d2b631c14ae744b2aacc7b099060961a,
title = "CD8+T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection",
abstract = "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 Tregcells 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.",
author = "Guang Xu and Mendell, {Nicole L.} and Yuejin Liang and Thomas Shelite and Yenny Goez-Rivillas and Lynn Soong and Donald Bouyer and David Walker",
year = "2017",
month = "7",
day = "19",
doi = "10.1371/journal.pntd.0005763",
language = "English (US)",
volume = "11",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "7",

}

TY - JOUR

T1 - CD8+T cells provide immune protection against murine disseminated endotheliotropic Orientia tsutsugamushi infection

AU - Xu, Guang

AU - Mendell, Nicole L.

AU - Liang, Yuejin

AU - Shelite, Thomas

AU - Goez-Rivillas, Yenny

AU - Soong, Lynn

AU - Bouyer, Donald

AU - Walker, David

PY - 2017/7/19

Y1 - 2017/7/19

N2 - 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 Tregcells 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.

AB - 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 Tregcells 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.

UR - http://www.scopus.com/inward/record.url?scp=85026789281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026789281&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0005763

DO - 10.1371/journal.pntd.0005763

M3 - Article

VL - 11

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 7

M1 - e0005763

ER -