Introduction: Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection that significantly impacts disease pathogenesis. However, in-depth studies characterizing the immunological landscape of the ectocervix during chronic HIV infection remain scarce despite the importance of this tissue site for HIV transmission. Methods: Ectocervical tissue samples were obtained from antiretroviral-naïve HIV-seropositive and -seronegative Kenyan female sex workers. Sampeling aimed for the follicular phase of the menstrual cycle. These samples were assessed by spatial transcriptomics and Gene Set Enrichment Analysis. We further performed multi-epitope ligand cartography (MELC) using an in situ staining panel that included 17 markers of primarily T cell–mediated immune responses. Results: Spatial transcriptomics revealed tissue-wide immune activation encompassing immune responses associated with chronic HIV infection. First, both the epithelial and submucosal compartments showed diverse but significant upregulation of humoral immune responses, as indicated by the expression of several antibody-related genes. Second, an antiviral state–associated cellular immunity was also observed in the HIV-seropositive group, characterized by upregulation of genes involved in interferon signaling across the mucosal tissue and a more spatially restricted mucosal expression of genes related to T cell activity and effector functions relative to the HIV-seronegative group. Additionally, HIV associated structural alterations were evident within both compartments. Downregulated genes across the epithelium were mainly linked to epithelial integrity, with the outer layer involved in terminal differentiation and the inner layer associated with epithelial structure. MELC analysis further revealed a significantly increased ectocervical leukocyte population in HIV-seropositive participants, primarily driven by an increase in CD8+ T cells while the CD4+ T cell population remained stable. Consistent with our spatial transcriptomics data, T cells from HIV-seropositive participants showed an increased effector phenotype, defined by elevated expression of various granzymes. Conclusion: By combining spatial transcriptomics and MELC, we identified significant HIV-associated cervical immune activity driven by induction of both T and B cell activity, together with a general antiviral state characterized by sustained interferon induction. These findings underscore that chronic HIV infection is associated with an altered ectocervical mucosal immune landscape years after primary infection. This sheds light on HIV pathogenesis at distant local sites and complements current knowledge on HIV-associated systemic immune activation.
from sddb import Catalog
cohort = Catalog().collection("geo-gse290350")
cohort.members # the 10 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse290350")
coll.ordered_artifacts.to_dataframe() # the 10 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse290350 --dest data/Licenses: 10 NCBI GEO policy
No linked publication found — please cite the data source.