Sustained immune activation and impaired epithelial barrier integrity in the ectocervix of women with chronic HIV infection.

Autor: Franzén Boger M; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Hasselrot T; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Kaldhusdal V; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Miranda GHB; Division of Computational Science and Technology, KTH Royal Institute of Technology, Stockholm, Sweden.; BioImage Informatics Facility, Science for Life Laboratory, Solna, Sweden., Czarnewski P; Science for Life Laboratory, Department of Biochemistry and Biophysics and National Bioinformatics Infrastructure Sweden, Stockholm University, Stockholm, Sweden., Edfeldt G; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Bradley F; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Rexaj G; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Lajoie J; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada., Omollo K; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya., Kimani J; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya.; Partners for Health and Development in Africa, Nairobi, Kenya., Fowke KR; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.; Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya.; Partners for Health and Development in Africa, Nairobi, Kenya.; Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada., Broliden K; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden., Tjernlund A; Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Nov 19; Vol. 20 (11), pp. e1012709. Date of Electronic Publication: 2024 Nov 19 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1012709
Abstrakt: Chronic systemic immune activation significantly influences human immunodeficiency virus (HIV) disease progression. Despite evidence of a pro-inflammatory environment in the genital tract of HIV-infected women, comprehensive investigations into cervical tissue from this region remain limited. Similarly, the consequences of chronic HIV infection on the integrity of the female genital epithelium are poorly understood, despite its importance in HIV transmission and replication. Ectocervical biopsies were obtained from HIV-seropositive (n = 14) and HIV-seronegative (n = 47) female Kenyan sex workers. RNA sequencing and bioimage analysis of epithelial junction proteins (E-cadherin, desmoglein-1, claudin-1, and zonula occludens-1) were conducted, along with CD4 staining. RNA sequencing revealed upregulation of immunoregulatory genes in HIV-seropositive women, primarily associated with heightened T cell activity and interferon signaling, which further correlated with plasma viral load. Transcription factor analysis confirmed the upregulation of pro-inflammatory transcription factors, such as RELA, NFKB1, and IKZF3, which facilitates HIV persistence in T cells. Conversely, genes and pathways associated with epithelial barrier function and structure were downregulated in the context of HIV. Digital bioimage analysis corroborated these findings, revealing significant disruption of various epithelial junction proteins in ectocervical tissues of the HIV-seropositive women. Thus, chronic HIV infection associated with ectocervical inflammation, characterized by induced T cell responses and interferon signaling, coupled with epithelial disruption. These alterations may influence HIV transmission and heighten susceptibility to other sexually transmitted infections. These findings prompt exploration of therapeutic interventions to address HIV-related complications and mitigate the risk of sexually transmitted infection transmission.
Competing Interests: P. Cz. is currently employed at DeepLife, located in 75013 Paris, France. None of the other authors declare any conflicts of interest.
(Copyright: © 2024 Franzén Boger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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