| Autor: |
Franzén Boger, Mathias, Hasselrot, Tyra, Kaldhusdal, Vilde, Miranda, Gisele H. B., Czarnewski, Paulo, Edfeldt, Gabriella, Bradley, Frideborg, Rexaj, Genta, Lajoie, Julie, Omollo, Kenneth, Kimani, Joshua, Fowke, Keith R., Broliden, Kristina, Tjernlund, Annelie |
| Zdroj: |
PLoS Pathogens; 11/19/2024, Vol. 20 Issue 11, p1-29, 29p |
| 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. Author summary: Chronic immune activation is a key feature of human immunodeficiency virus (HIV) infection and is linked to various health issues, including sexually transmitted infections. The consequence of immune activation is becoming evident as age-related morbidities are appearing in younger people living with HIV. The female genital tract is a primary location for initial HIV infection and replication following sexual transmission. While we know that chronic HIV infection causes inflammation in the tissue, more detailed studies, especially focusing on mucosal epithelial tissue, are still needed. To understand how chronic HIV infection affects the female genital tract, we examined samples from HIV-positive and HIV-negative Kenyan female sex workers. We found that chronic HIV infection is associated with a sustained cervical inflammatory environment. We also noticed a decrease in genes responsible for maintaining the protective epithelial barrier in the tissue. Our results suggest a connection between HIV-induced immune responses in mucosal areas and the health of the tissue, which might explain why HIV infection may increase the risk of other sexually transmitted infections. This highlights the importance of enhancing mucosal health in people living with chronic HIV to reduce associated complications. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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