Research Topic

Balanced and Unbalanced Immune Response to Dengue Virus in Disease Protection and Pathogenesis

About this Research Topic

The ongoing pandemic has highlighted a central principle of the host immune response to RNA virus infections: while most infected patients remain asymptomatic or mild symptomatic, a portion of patients experiences severe clinical symptoms, suggesting the existence of host immune factors that determine susceptibility to symptomatic disease. One well-known RNA virus infection that is characterized by differential susceptibility to symptomatic disease due to host immune determinants is dengue. Whereas a well-balanced, early immune response is protective for the host and leads to asymptomatic infection or self-limiting disease, exacerbated and skewed immune responses can result in dengue hemorrhagic fever or dengue shock syndrome.

Currently, dengue is the most significant vector-borne viral disease in humans. Dengue is caused by dengue virus (DENV), a positive sense, single-stranded RNA virus belonging to the Flaviviridae family, and is transmitted by Aedes mosquitoes. DENV strains are classified into four antigenically distinct serotypes, DENV-1 to -4.

The mechanisms that result in a balanced immune response leading to viral clearance without the concomitant occurrence of immunopathology are not well defined. Early innate defense mechanisms to the virus and components of the mosquito saliva in the skin environment shape the subsequent immune response. Dendritic cells and macrophages are direct targets of the virus and contribute to virus spread. The more severe forms of dengue occur mainly after re-infection with a different serotype. Antibody-dependent enhancement (ADE), whereby pre-existing antibodies facilitate infection of FcγR-bearing cells, has been identified as potential mechanism to explain this epidemiological observation. Here, either altered cellular immune response due to FcγR triggering and/or increased viral load could contribute to immunopathology. Although seroneutralization is important for virus containment, studies suggest that waning anti-dengue antibody concentrations and/or antibodies directed against specific epitopes on the viral surface could induce ADE, demonstrating the dual role of the humoral response in dengue pathogenesis and protection. In addition, the role of CD4+ and CD8+ T cells during infection remains elusive. There is ample evidence that these cells play an important protective role during dengue infection. On the other hand, pre-existing memory T cells can alter the kinetics and specificity of the immune response during a secondary infection as observed during original antigenic sin.

We seek Original Research Articles, Reviews, Opinion and Perspective articles. We welcome research resulting from basic science, in vivo animal models, and clinical studies. Subjects include (but are not limited to):

1. Mechanisms of balanced and unbalanced innate and adaptive immune responses to dengue virus infection
2. The development of novel vaccine candidates
3. The identification of correlates of protection or immunopathology


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The ongoing pandemic has highlighted a central principle of the host immune response to RNA virus infections: while most infected patients remain asymptomatic or mild symptomatic, a portion of patients experiences severe clinical symptoms, suggesting the existence of host immune factors that determine susceptibility to symptomatic disease. One well-known RNA virus infection that is characterized by differential susceptibility to symptomatic disease due to host immune determinants is dengue. Whereas a well-balanced, early immune response is protective for the host and leads to asymptomatic infection or self-limiting disease, exacerbated and skewed immune responses can result in dengue hemorrhagic fever or dengue shock syndrome.

Currently, dengue is the most significant vector-borne viral disease in humans. Dengue is caused by dengue virus (DENV), a positive sense, single-stranded RNA virus belonging to the Flaviviridae family, and is transmitted by Aedes mosquitoes. DENV strains are classified into four antigenically distinct serotypes, DENV-1 to -4.

The mechanisms that result in a balanced immune response leading to viral clearance without the concomitant occurrence of immunopathology are not well defined. Early innate defense mechanisms to the virus and components of the mosquito saliva in the skin environment shape the subsequent immune response. Dendritic cells and macrophages are direct targets of the virus and contribute to virus spread. The more severe forms of dengue occur mainly after re-infection with a different serotype. Antibody-dependent enhancement (ADE), whereby pre-existing antibodies facilitate infection of FcγR-bearing cells, has been identified as potential mechanism to explain this epidemiological observation. Here, either altered cellular immune response due to FcγR triggering and/or increased viral load could contribute to immunopathology. Although seroneutralization is important for virus containment, studies suggest that waning anti-dengue antibody concentrations and/or antibodies directed against specific epitopes on the viral surface could induce ADE, demonstrating the dual role of the humoral response in dengue pathogenesis and protection. In addition, the role of CD4+ and CD8+ T cells during infection remains elusive. There is ample evidence that these cells play an important protective role during dengue infection. On the other hand, pre-existing memory T cells can alter the kinetics and specificity of the immune response during a secondary infection as observed during original antigenic sin.

We seek Original Research Articles, Reviews, Opinion and Perspective articles. We welcome research resulting from basic science, in vivo animal models, and clinical studies. Subjects include (but are not limited to):

1. Mechanisms of balanced and unbalanced innate and adaptive immune responses to dengue virus infection
2. The development of novel vaccine candidates
3. The identification of correlates of protection or immunopathology


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

08 November 2020 Abstract
17 February 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

08 November 2020 Abstract
17 February 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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