Poster Session 1
Category: Infectious Diseases
Poster Session 1
Christine A. Blauvelt, MD
Assistant Professor
University of California, San Francisco
San Francisco, California, United States
Nida Ozarslan, MD
University of California, San Francisco
San Francisco, California, United States
John Ategeka, BS
Infectious Diseases Research Collaboration
Kampala, Kampala, Uganda
Megan Chidboy
University of California, San Francisco
San Francisco, California, United States
Sirirak Buarpung, PhD
University of California, San Francisco
San Francisco, California, United States
Jimmy Kizza, MD
Infectious Diseases Research Collaboration
Kampala, Kampala, Uganda
Abel Kakuru, MD, PhD
Infectious Diseases Research Collaboration
Kampala, Kampala, Uganda
Moses R. Kamya, MD, PhD
Infectious Diseases Research Collaboration
Kampala, Kampala, Uganda
Grant Dorsey, MD, PhD
University of California, San Francisco
San Francisco, California, United States
Phillip J. Rosenthal, MD
Professor
University of California, San Francisco
San Francisco, California, United States
Joshua F. Robinson, PhD
Associate Professor
University of California, San Francisco
San Francisco, California, United States
.jpg "Stephanie L. Gaw, MD, PhD photo")
Stephanie L. Gaw, MD, PhD
Associate Professor
University of California, San Francisco
San Francisco, California, United States
Placental malaria (PM) is due to sequestration of Plasmodium falciparum-infected red blood cells in placental intervillous spaces and subsequent inflammatory responses. The impact of PM on Hofbauer cells (HBCs) and consequences for placental function and fetal immune development remain poorly understood. This study aimed to define transcriptional alterations in HBCs in past-chronic PM.
Study Design:
We conducted a nested case-control study within a randomized controlled phase III trial in Uganda (NCT04336189), investigating intermittent preventative treatment for malaria in pregnancy. PM status was determined by Rogerson criteria. Formalin-fixed paraffin-embedded placental tissue samples from pregnancies with past-chronic PM (n=4) and healthy controls (n=7) were profiled using the NanoString GeoMx Digital Spatial Profiler. Regions of interest from placental villi were segmented to enrich for HBCs using CD68 immunofluorescence. Spatial RNA sequencing was performed on segmented HBCs, followed by differential gene expression and pathway enrichment analyses.
Results:
Patient characteristics were similar between groups, including maternal age, gestational age at delivery, and fetal sex. Transcriptomic profiling identified 463 differentially expressed genes in HBCs from PM-exposed placentas vs controls (Figure 1; unadj p< 0.05 and abs FC >1.5). Past-chronic PM samples exhibited upregulation of genes associated with interferon-driven antipathogen responses (MX1, IFI27), and downregulation of immunoregulatory signaling (IL27), angiogenic remodeling (PDGFD), and cellular stress responsiveness (TP73). GSEA pathway enrichment analysis revealed significant enrichment in interferon signaling, antiviral response, antigen processing and presentation, and cellular metabolism pathways (Figure 2; adj p< 0.01).
Conclusion:
Our findings suggest that past-chronic PM exposure is associated with persistent transcriptional reprogramming of fetal HBCs. Further studies are needed to elucidate how these changes affect placental vascular remodeling, fetal immune programming, and risk of adverse obstetric and neonatal outcomes.