Functional Characterisation of Surfactant Protein A as a Novel Prophylactic Means against Oncogenic HPV Infections

Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant pr...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-07, Vol.25 (14), p.7712
Main Authors: Carse, Sinead, Reid, Tim, Madsen, Jens, Clark, Howard, Kirjakulov, Artur, Bergant Marušič, Martina, Schäfer, Georgia
Format: Article
Language:English
Subjects:
Cervical cancer
Cytokines
Dendritic cells
HPV prophylactic
Human papillomavirus
human papillomavirus (HPV)
Immune system
Infections
Pathogens
Proteins
pseudovirus
surfactant protein A (SP-A)
Surfactants
THP-1-derived immune cells
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Summary:Human papillomavirus (HPV) infection poses a significant health challenge, particularly in low- and middle-income countries (LMIC), where limited healthcare access and awareness hinder vaccine accessibility. To identify alternative HPV targeting interventions, we previously reported on surfactant protein A (SP-A) as a novel molecule capable of recognising HPV16 pseudovirions (HPV16-PsVs) and reducing infection in a murine cervicovaginal HPV challenge model. Building on these findings, our current study aimed to assess SP-A's suitability as a broad-spectrum HPV-targeting molecule and its impact on innate immune responses. We demonstrate SP-A's ability to agglutinate and opsonise multiple oncogenic HPV-PsVs types, enhancing their uptake and clearance by RAW264.7 murine macrophages and THP-1 human-derived immune cells. The SP-A opsonisation of HPV not only led to increased lysosomal accumulation in macrophages and HaCaT keratinocytes but also resulted in a decreased infection of HaCaT cells, which was further decreased when co-cultured with innate immune cells. An analysis of human innate immune cell cytokine profiles revealed a significant inflammatory response upon SP-A exposure, potentially contributing to the overall inhibition of HPV infection. These results highlight the multi-layered impact of SP-A on HPV, innate immune cells and keratinocytes and lay the basis for the development of alternative prophylactic interventions against diverse HPV types.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25147712