Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage

Research output: Contribution to journalArticle

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Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. / Dunn, C; Brunetto, M; Reynolds, G; Christophides, T; Kennedy, PT; Lampertico, P; [No Value], [No Value]; Lopes, AR; Borrow, P; Williams, KT; Humphreys, Elizabeth; Afford, Simon; Adams, David; Bertoletti, A; Maini, MK.

In: The Journal of Experimental Medicine, Vol. 204, No. 3, 20.02.2007, p. 667-680.

Research output: Contribution to journalArticle

Harvard

Dunn, C, Brunetto, M, Reynolds, G, Christophides, T, Kennedy, PT, Lampertico, P, [No Value], NV, Lopes, AR, Borrow, P, Williams, KT, Humphreys, E, Afford, S, Adams, D, Bertoletti, A & Maini, MK 2007, 'Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage', The Journal of Experimental Medicine, vol. 204, no. 3, pp. 667-680. https://doi.org/10.1084/jem.20061287

APA

Dunn, C., Brunetto, M., Reynolds, G., Christophides, T., Kennedy, PT., Lampertico, P., [No Value], N. V., Lopes, AR., Borrow, P., Williams, KT., Humphreys, E., Afford, S., Adams, D., Bertoletti, A., & Maini, MK. (2007). Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. The Journal of Experimental Medicine, 204(3), 667-680. https://doi.org/10.1084/jem.20061287

Vancouver

Author

Dunn, C ; Brunetto, M ; Reynolds, G ; Christophides, T ; Kennedy, PT ; Lampertico, P ; [No Value], [No Value] ; Lopes, AR ; Borrow, P ; Williams, KT ; Humphreys, Elizabeth ; Afford, Simon ; Adams, David ; Bertoletti, A ; Maini, MK. / Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. In: The Journal of Experimental Medicine. 2007 ; Vol. 204, No. 3. pp. 667-680.

Bibtex

@article{8ee1f7ed46b4462a8e14607c0a0a19b2,
title = "Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage",
abstract = "Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-alpha, and natural killer (NK) cell expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death-inducing receptor. IFN-alpha concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-alpha/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen-specific mechanism can be switched on by cytokines produced during active HBV infection.",
author = "C Dunn and M Brunetto and G Reynolds and T Christophides and PT Kennedy and P Lampertico and {[No Value]}, {[No Value]} and AR Lopes and P Borrow and KT Williams and Elizabeth Humphreys and Simon Afford and David Adams and A Bertoletti and MK Maini",
year = "2007",
month = feb,
day = "20",
doi = "10.1084/jem.20061287",
language = "English",
volume = "204",
pages = "667--680",
journal = "The Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage

AU - Dunn, C

AU - Brunetto, M

AU - Reynolds, G

AU - Christophides, T

AU - Kennedy, PT

AU - Lampertico, P

AU - [No Value], [No Value]

AU - Lopes, AR

AU - Borrow, P

AU - Williams, KT

AU - Humphreys, Elizabeth

AU - Afford, Simon

AU - Adams, David

AU - Bertoletti, A

AU - Maini, MK

PY - 2007/2/20

Y1 - 2007/2/20

N2 - Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-alpha, and natural killer (NK) cell expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death-inducing receptor. IFN-alpha concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-alpha/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen-specific mechanism can be switched on by cytokines produced during active HBV infection.

AB - Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-alpha, and natural killer (NK) cell expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death-inducing receptor. IFN-alpha concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-alpha/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen-specific mechanism can be switched on by cytokines produced during active HBV infection.

UR - http://www.scopus.com/inward/record.url?scp=33947411395&partnerID=8YFLogxK

U2 - 10.1084/jem.20061287

DO - 10.1084/jem.20061287

M3 - Article

C2 - 17353365

VL - 204

SP - 667

EP - 680

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -