Mobilization and Activation of the Innate Immune Response to Dengue Virus

King, Christine A.; Wegman, Adam D.; Endy, Timothy P.

doi:10.3389/fcimb.2020.574417

Cited by 34 publications

(35 citation statements)

References 190 publications

(223 reference statements)

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“…Secondary heterotypic infection is associated with an increased chance of developing severe disease ( 10 , 11 ), likely due to pathogenic memory T and B cell response from previous infection known as T cell antigenic sin ( 9 , 12 , 13 ) and antibody-dependent enhancement ( 14 , 15 ). Innate and innate-like responses to DENV infection are not only crucial as the first line of defense but also influence subsequent adaptive T and B cell responses ( 16 ). Beside the role of innate-like T cells, NKT ( 17 – 19 ) and MAITs ( 20 , 21 ), several lines of evidence suggested the important roles of various innate responses in DENV infection and viral evasion strategies, in particular type I IFN ( 22 – 24 ), monocytes, macrophages and dendritic cells ( 25 ), mast cells ( 18 , 26 ), as well as NK cells ( 27 ).…”

Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

et al. 2021

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BackgroundDengue virus (DENV) infection has a global impact on public health. The clinical outcomes (of DENV) can vary from a flu-like illness called dengue fever (DF), to a more severe form, known as dengue hemorrhagic fever (DHF). The underlying innate immune mechanisms leading to protective or detrimental outcomes have not been fully elucidated. Helper innate lymphoid cells (hILCs), an innate lymphocyte recently discovered, functionally resemble T-helper cells and are important in inflammation and homeostasis. However, the role of hILCs in DENV infection had been unexplored.MethodsWe performed flow cytometry to investigate the frequency and phenotype of hILCs in peripheral blood mononuclear cells from DENV-infected patients of different disease severities (DF and DHF), and at different phases (febrile and convalescence) of infection. Intracellular cytokine staining of hILCs from DF and DHF were also evaluated by flow cytometry after ex vivo stimulation. Further, the hILCs were sorted and subjected to transcriptome analysis using RNA sequencing. Differential gene expression analysis was performed to compare the febrile and convalescent phase samples in DF and DHF. Selected differentially expressed genes were then validated by quantitative PCR.ResultsPhenotypic analysis showed marked activation of all three hILC subsets during the febrile phase as shown by higher CD69 expression when compared to paired convalescent samples, although the frequency of hILCs remained unchanged. Upon ex vivo stimulation, hILCs from febrile phase DHF produced significantly higher IFN-γ and IL-4 when compared to those of DF. Transcriptomic analysis showed unique hILCs gene expression in DF and DHF, suggesting that divergent functions of hILCs may be associated with different disease severities. Differential gene expression analysis indicated that hILCs function both in cytokine secretion and cytotoxicity during the febrile phase of DENV infection.ConclusionsHelper ILCs are activated in the febrile phase of DENV infection and display unique transcriptomic changes as well as cytokine production that correlate with severity. Targeting hILCs during early innate response to DENV might help shape subsequent immune responses and potentially lessen the disease severity in the future.

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Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

et al. 2021

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“…Flaviviruses cause globally relevant epidemics in humans, infecting up to 400 million people annually [ 33 ]. Dengue virus (DENV), classified in four serotypes and currently endemic in more than 100 countries [ 38 ], can cause a wide spectrum of disease manifestations ranging from a subclinical self-limited infection or a mild febrile illness termed dengue fever, to a life-threatening dengue hemorrhagic fever and dengue shock syndrome, especially after secondary infections with an heterologous serotype [ 39 ]. Zika virus (ZIKV) spread throughout the American continent in 2015 causing considerable worldwide social and medical alarm due to its association with congenital disorders [ 29 ], such as microcephaly in newborns, or severe neurological manifestations in adults [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections

Blázquez

Saiz

2020

IJMS

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Protein kinases (PKs) are enzymes that catalyze the transfer of the terminal phosphate group from ATP to a protein acceptor, mainly to serine, threonine, and tyrosine residues. PK catalyzed phosphorylation is critical to the regulation of cellular signaling pathways that affect crucial cell processes, such as growth, differentiation, and metabolism. PKs represent attractive targets for drugs against a wide spectrum of diseases, including viral infections. Two different approaches are being applied in the search for antivirals: compounds directed against viral targets (direct-acting antivirals, DAAs), or against cellular components essential for the viral life cycle (host-directed antivirals, HDAs). One of the main drawbacks of DAAs is the rapid emergence of drug-resistant viruses. In contrast, HDAs present a higher barrier to resistance development. This work reviews the use of chemicals that target cellular PKs as HDAs against virus of the Flaviviridae family (Flavivirus and Hepacivirus), thus being potentially valuable therapeutic targets in the control of these pathogens.

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“…DENV is inoculated by the mosquito vector into the skin epidermis where it encounters permissive skin-resident cells such as keratinocytes, fibroblasts, mast cells and immature dendritic cells (langerhans cells) [ 11 ]. These cells migrate to lymphoid organs, favoring its dissemination to peripheral blood mononuclear cells (PBMCs) and tissues.…”

Section: The Dengue Virus Life Cyclementioning

confidence: 99%

Innate Immune Response to Dengue Virus: Toll-like Receptors and Antiviral Response

Fernandes-Santos

Azeredo

2022

Viruses

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Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV1-4). The clinical manifestations range from asymptomatic to life-threatening dengue hemorrhagic fever (DHF) and/or Dengue Shock Syndrome (DSS). Viral and host factors are related to the clinical outcome of dengue, although the disease pathogenesis remains uncertain. The innate antiviral response to DENV is implemented by a variety of immune cells and inflammatory mediators. Blood monocytes, dendritic cells (DCs) and tissue macrophages are the main target cells of DENV infection. These cells recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs). Pathogen recognition is a critical step in eliciting the innate immune response. Toll-like receptors (TLRs) are responsible for the innate recognition of pathogens and represent an essential component of the innate and adaptive immune response. Ten different TLRs are described in humans, which are expressed in many different immune cells. The engagement of TLRs with viral PAMPs triggers downstream signaling pathways leading to the production of inflammatory cytokines, interferons (IFNs) and other molecules essential for the prevention of viral replication. Here, we summarize the crucial TLRs’ roles in the antiviral innate immune response to DENV and their association with viral pathogenesis.

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Mobilization and Activation of the Innate Immune Response to Dengue Virus

Cited by 34 publications

References 190 publications

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

Innate Lymphoid Cells Activation and Transcriptomic Changes in Response to Human Dengue Infection

Potential for Protein Kinase Pharmacological Regulation in Flaviviridae Infections

Innate Immune Response to Dengue Virus: Toll-like Receptors and Antiviral Response

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