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: | , , , , , , |
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| Format: | Bài trích |
| Language: | English |
| Published: |
American Society for Microbiology
2022
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| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/jvi.01850-21 https://dlib.phenikaa-uni.edu.vn/handle/PNK/5735 https://doi.org/10.1128/jvi.01850-21 |
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| Summary: | 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 |
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