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Immune-mediated cytokine storm and its role in severe dengue

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Abstract

Dengue remains one of the most important mosquito-borne diseases worldwide. Infection with one of the serologically related dengue viruses (DENVs) can lead to a wide range of clinical manifestations and severity. Severe dengue is characterized by plasma leakage and abnormal bleeding that can lead to shock and death. There is currently no specific treatment for severe dengue due to gaps in understanding of the underlying mechanisms. The transient period of vascular leakage is usually followed by a rapid recovery and is suggestive of the effects of short-lived biological mediators. Both the innate and the adaptive immune systems are activated in severe dengue and contribute to the cytokine production. We discuss the immunological events elicited during a DENV infection and identify candidate cytokines that may play a key role in the severe manifestations of dengue and possible interventions.

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Abbreviations

CLEC5A:

C-type lectin domain family 5 member A

DC-SIGN:

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

DENV:

Dengue virus

DF:

Dengue fever

DHF:

Dengue hemorrhagic fever

IFN:

Interferon

IL:

Interleukin

MCP:

Monocyte chemotactic factor

MIF:

Migration inhibition factor

MMP:

Matrix metalloproteases

NS:

Nonstructural

VE-cadherin:

Vascular endothelial cadherin

VEGF-A:

Vascular endothelial growth factor-A

VEGFR1:

Vascular endothelial growth factor receptor 1

VEGFR2:

Vascular endothelial growth factor receptor 2

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Acknowledgements

This work was supported in part by the National Institutes of Health (grant P01 AI034533). The opinions expressed are those of the authors and do not represent the official position of the National Institutes of Health.

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  1. Institute for Immunology and Informatics, University of Rhode Island, 80 Washington St., Rm 302F, Providence, RI, 02903, USA

    Anon Srikiatkhachorn, Anuja Mathew & Alan L. Rothman

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  1. Anon Srikiatkhachorn
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  2. Anuja Mathew
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Correspondence to Anon Srikiatkhachorn.

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This article is a contribution to the special issue on Cytokine Storm in Infectious Diseases -- Guest Editor: John Teijaro

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Srikiatkhachorn, A., Mathew, A. & Rothman, A.L. Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol 39, 563–574 (2017). https://doi.org/10.1007/s00281-017-0625-1

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