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Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells

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Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells. / Dias, Joana; Hengst, Julia; Parrot, Tiphaine; Leeansyah, Edwin; Lunemann, Sebastian; Malone, David F.G.; Hardtke, Svenja; Strauss, Otto; Zimmer, Christine L.; Berglin, Lena; Schirdewahn, Thomas; Ciesek, Sandra ; Marquardt, Nicole; von Hahn, Thomas; Manns, Michael P; Cornberg, Markus; Ljunggren, Hans-Gustaf; Wedemeyer, Heiner; Sandberg, Johan K.; Björkström, Niklas K.

In: J HEPATOL, Vol. 71, No. 2, 08.2019, p. 301-312.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dias, J, Hengst, J, Parrot, T, Leeansyah, E, Lunemann, S, Malone, DFG, Hardtke, S, Strauss, O, Zimmer, CL, Berglin, L, Schirdewahn, T, Ciesek, S, Marquardt, N, von Hahn, T, Manns, MP, Cornberg, M, Ljunggren, H-G, Wedemeyer, H, Sandberg, JK & Björkström, NK 2019, 'Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells', J HEPATOL, vol. 71, no. 2, pp. 301-312. https://doi.org/10.1016/j.jhep.2019.04.009

APA

Dias, J., Hengst, J., Parrot, T., Leeansyah, E., Lunemann, S., Malone, D. F. G., Hardtke, S., Strauss, O., Zimmer, C. L., Berglin, L., Schirdewahn, T., Ciesek, S., Marquardt, N., von Hahn, T., Manns, M. P., Cornberg, M., Ljunggren, H-G., Wedemeyer, H., Sandberg, J. K., & Björkström, N. K. (2019). Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells. J HEPATOL, 71(2), 301-312. https://doi.org/10.1016/j.jhep.2019.04.009

Vancouver

Dias J, Hengst J, Parrot T, Leeansyah E, Lunemann S, Malone DFG et al. Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells. J HEPATOL. 2019 Aug;71(2):301-312. https://doi.org/10.1016/j.jhep.2019.04.009

Bibtex

@article{f51952653f194c1e871a48ba5c42ea52,
title = "Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells",
abstract = "BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.METHODS: MAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls.RESULTS: Circulating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection.CONCLUSIONS: These results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses.LAY SUMMARY: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.",
author = "Joana Dias and Julia Hengst and Tiphaine Parrot and Edwin Leeansyah and Sebastian Lunemann and Malone, {David F.G.} and Svenja Hardtke and Otto Strauss and Zimmer, {Christine L.} and Lena Berglin and Thomas Schirdewahn and Sandra Ciesek and Nicole Marquardt and {von Hahn}, Thomas and Manns, {Michael P} and Markus Cornberg and Hans-Gustaf Ljunggren and Heiner Wedemeyer and Sandberg, {Johan K.} and Bj{\"o}rkstr{\"o}m, {Niklas K}",
note = "Copyright {\textcopyright} 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2019",
month = aug,
doi = "10.1016/j.jhep.2019.04.009",
language = "English",
volume = "71",
pages = "301--312",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells

AU - Dias, Joana

AU - Hengst, Julia

AU - Parrot, Tiphaine

AU - Leeansyah, Edwin

AU - Lunemann, Sebastian

AU - Malone, David F.G.

AU - Hardtke, Svenja

AU - Strauss, Otto

AU - Zimmer, Christine L.

AU - Berglin, Lena

AU - Schirdewahn, Thomas

AU - Ciesek, Sandra

AU - Marquardt, Nicole

AU - von Hahn, Thomas

AU - Manns, Michael P

AU - Cornberg, Markus

AU - Ljunggren, Hans-Gustaf

AU - Wedemeyer, Heiner

AU - Sandberg, Johan K.

AU - Björkström, Niklas K

N1 - Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2019/8

Y1 - 2019/8

N2 - BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.METHODS: MAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls.RESULTS: Circulating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection.CONCLUSIONS: These results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses.LAY SUMMARY: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.

AB - BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.METHODS: MAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls.RESULTS: Circulating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection.CONCLUSIONS: These results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses.LAY SUMMARY: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.

U2 - 10.1016/j.jhep.2019.04.009

DO - 10.1016/j.jhep.2019.04.009

M3 - SCORING: Journal article

C2 - 31100314

VL - 71

SP - 301

EP - 312

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 2

ER -