Adenovirus-α-defensin complexes induce NLRP3-associated maturation of human phagocytes via TLR4 engagement

Eichholz, K.; Tran, H. T.; Cheneau, C.; Tran, T. T. P.; Paris, O.; Pugniere, M.; Kremer, E. J.

doi:10.1101/2021.10.26.465098

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bioRxiv · 10.1101/2021.10.26.465098

Adenovirus-α-defensin complexes induce NLRP3-associated maturation of human phagocytes via TLR4 engagement

Eichholz, K.·Tran, H. T.·Cheneau, C.·Tran, T. T. P.·Paris, O.·Pugniere, M.·Kremer, E. J.

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Abstract

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 hr is poorly understood. In this study, we asked if human neutrophil protein 1 (HNP-1), an -defensin that influences the direct and indirect innate immune responses to a range of pathogens, impacts the innate response of human phagocytes to three HAdV species/types (HAdV-C5, -D26, -B35). We show that HNP-1 binds to the capsids, redirects HAdV-C5, -D26, -B35 to Toll-like receptor 4 (TLR4), which leads to internalization, an NLRP3-mediated inflammasome response, and IL-1{beta} release. Surprisingly, IL-1{beta} release was not associated with notable disruption of plasma membrane integrity. These data further our understanding of HAdV innate immunogenicity and may provide pathways to extend HAdV-based vaccines efficacy.

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Eichholz, K., Tran, H. T., Cheneau, C., Tran, T. T. P., Paris, O., Pugniere, M., Kremer, E. J.. 2021-10-26. Adenovirus-α-defensin complexes induce NLRP3-associated maturation of human phagocytes via TLR4 engagement. https://doi.org/10.1101/2021.10.26.465098

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