Dysfunctional Innate Immune Responses and Severe Dengue.
B cells
T cells
antibody dependent enhancement
dengue
endotoxin
innate immunity
mast cells
monocytes
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2020
2020
Historique:
received:
06
08
2020
accepted:
15
09
2020
entrez:
16
11
2020
pubmed:
17
11
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue.
Identifiants
pubmed: 33194836
doi: 10.3389/fcimb.2020.590004
pmc: PMC7644808
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
590004Subventions
Organisme : Medical Research Council
ID : G116/150
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137881017
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/5
Pays : United Kingdom
Informations de copyright
Copyright © 2020 Malavige, Jeewandara and Ogg.
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