Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement

Intramuscular delivery of human adenovirus (HAdV)-based vaccines leads to rapid recruitment of neutrophils, which then release antimicrobial peptides/proteins (AMPs). How these AMPs influence vaccine efficacy over the subsequent 24 h is poorly understood. In this study, we asked if human neutrophil...

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Main Authors: Karsten, Eichholz, Tuan Hiep, Tran, Coraline, Chéneau, Thi Thu Phuong, Tran, Océane, Paris
Format: Bài trích
Language:English
Published: American Society for Microbiology 2022
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Online Access:https://journals.asm.org/doi/10.1128/jvi.01850-21
https://dlib.phenikaa-uni.edu.vn/handle/PNK/5875
https://doi.org/10.1128/jvi.01850-21
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spelling oai:localhost:PNK-58752022-08-17T05:54:54Z Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement Karsten, Eichholz Tuan Hiep, Tran Coraline, Chéneau Thi Thu Phuong, Tran Océane, Paris Adenovirus-α-Defensin NLRP3-Associated Intramuscular delivery of human adenovirus (HAdV)-based vaccines leads to rapid recruitment of neutrophils, which then release antimicrobial peptides/proteins (AMPs). How these AMPs influence vaccine efficacy over the subsequent 24 h is poorly understood. In this study, we asked if human neutrophil protein 1 (HNP-1), an α-defensin that influences direct and indirect innate immune responses to a range of pathogens, impacts the response of human phagocytes to three HAdV species/types (HAdV-C5, -D26, -B35). We show that HNP-1 binds to the capsids and redirects HAdV-C5, -D26, and -B35 to Toll-like receptor 4 (TLR4), which leads to internalization, an NLRP3-mediated inflammasome response, and interleukin 1 beta (IL-1β) release. Surprisingly, IL-1β release was not associated with notable disruption of plasma membrane integrity. These data further our understanding of HAdV vaccine immunogenicity and may provide pathways to extend the efficacy. 2022-07-13T01:59:46Z 2022-07-13T01:59:46Z 2022 Bài trích https://journals.asm.org/doi/10.1128/jvi.01850-21 https://dlib.phenikaa-uni.edu.vn/handle/PNK/5875 https://doi.org/10.1128/jvi.01850-21 en American Society for Microbiology
institution Digital Phenikaa
collection Digital Phenikaa
language English
topic Adenovirus-α-Defensin
NLRP3-Associated
spellingShingle Adenovirus-α-Defensin
NLRP3-Associated
Karsten, Eichholz
Tuan Hiep, Tran
Coraline, Chéneau
Thi Thu Phuong, Tran
Océane, Paris
Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
description Intramuscular delivery of human adenovirus (HAdV)-based vaccines leads to rapid recruitment of neutrophils, which then release antimicrobial peptides/proteins (AMPs). How these AMPs influence vaccine efficacy over the subsequent 24 h is poorly understood. In this study, we asked if human neutrophil protein 1 (HNP-1), an α-defensin that influences direct and indirect innate immune responses to a range of pathogens, impacts the response of human phagocytes to three HAdV species/types (HAdV-C5, -D26, -B35). We show that HNP-1 binds to the capsids and redirects HAdV-C5, -D26, and -B35 to Toll-like receptor 4 (TLR4), which leads to internalization, an NLRP3-mediated inflammasome response, and interleukin 1 beta (IL-1β) release. Surprisingly, IL-1β release was not associated with notable disruption of plasma membrane integrity. These data further our understanding of HAdV vaccine immunogenicity and may provide pathways to extend the efficacy.
format Bài trích
author Karsten, Eichholz
Tuan Hiep, Tran
Coraline, Chéneau
Thi Thu Phuong, Tran
Océane, Paris
author_facet Karsten, Eichholz
Tuan Hiep, Tran
Coraline, Chéneau
Thi Thu Phuong, Tran
Océane, Paris
author_sort Karsten, Eichholz
title Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
title_short Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
title_full Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
title_fullStr Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
title_full_unstemmed Adenovirus-α-Defensin Complexes Induce NLRP3-Associated Maturation of Human Phagocytes via Toll-Like Receptor 4 Engagement
title_sort adenovirus-α-defensin complexes induce nlrp3-associated maturation of human phagocytes via toll-like receptor 4 engagement
publisher American Society for Microbiology
publishDate 2022
url https://journals.asm.org/doi/10.1128/jvi.01850-21
https://dlib.phenikaa-uni.edu.vn/handle/PNK/5875
https://doi.org/10.1128/jvi.01850-21
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score 8.881002