In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2022-10-14), p. e1010499-
Abstract:
Severe dengue virus (DENV) infection is characterized by exacerbated inflammatory responses that lead to endothelial dysfunction and plasma leakage. We have recently demonstrated that Toll-like receptor 2 (TLR2) on blood monocytes senses DENV infection leading to endothelial activation. Here, we report that non-infectious immature DENV particles, which are released in large numbers by DENV-infected cells, drive endothelial activation via the TLR2 axis. We show that fully immature DENV particles induce a rapid, within 6 hours post-infection, inflammatory response in PBMCs. Furthermore, pharmacological blocking of TLR2/TLR6/CD14 and/or NF-kB prior to exposure of PBMCs to immature DENV reduces the initial production of inter alia TNF-α and IL-1β by monocytes and prevents endothelial activation. However, prolonged TLR2 block induces TNF-α production and leads to exacerbated endothelial activation, indicating that TLR2-mediated responses play an important role not only in the initiation but also the resolution of inflammation. Altogether, these data indicate that the maturation status of the virus has the potential to influence the kinetics and extent of inflammatory responses during DENV infection.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010499
DOI:
10.1371/journal.ppat.1010499.g001
DOI:
10.1371/journal.ppat.1010499.g002
DOI:
10.1371/journal.ppat.1010499.g003
DOI:
10.1371/journal.ppat.1010499.g004
DOI:
10.1371/journal.ppat.1010499.g005
DOI:
10.1371/journal.ppat.1010499.g006
DOI:
10.1371/journal.ppat.1010499.g007
DOI:
10.1371/journal.ppat.1010499.g008
DOI:
10.1371/journal.ppat.1010499.s001
DOI:
10.1371/journal.ppat.1010499.s002
DOI:
10.1371/journal.ppat.1010499.s003
DOI:
10.1371/journal.ppat.1010499.s004
DOI:
10.1371/journal.ppat.1010499.s005
DOI:
10.1371/journal.ppat.1010499.s006
DOI:
10.1371/journal.ppat.1010499.s007
DOI:
10.1371/journal.ppat.1010499.s008
DOI:
10.1371/journal.ppat.1010499.s009
DOI:
10.1371/journal.ppat.1010499.s010
DOI:
10.1371/journal.ppat.1010499.s011
DOI:
10.1371/journal.ppat.1010499.s012
DOI:
10.1371/journal.ppat.1010499.s013
DOI:
10.1371/journal.ppat.1010499.s014
DOI:
10.1371/journal.ppat.1010499.s015
DOI:
10.1371/journal.ppat.1010499.s016
DOI:
10.1371/journal.ppat.1010499.r001
DOI:
10.1371/journal.ppat.1010499.r002
DOI:
10.1371/journal.ppat.1010499.r003
DOI:
10.1371/journal.ppat.1010499.r004
DOI:
10.1371/journal.ppat.1010499.r005
DOI:
10.1371/journal.ppat.1010499.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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