Date of Award

Spring 6-30-2025

Degree Type

Honors Thesis

Major

Biology

Degree Name

Bachelor of Science

Department

Biology

First Advisor

Dr. Stephanie Gaw

Second Advisor

Dr. Christina Tzagarakis-Foster

Third Advisor

Professor Leslie King

Abstract

Malaria remains a prevalent infectious disease that continues to cause disease-related morbidity and mortality. Despite preventative efforts, malarial pregnancies still cause birth complications, therefore emphasizing the necessity to study these adverse outcomes in malarial pregnancy. Malaria in pregnancy can lead to placental malaria (PM), which is the presence and accumulation of Plasmodium-infected red blood cells in the placental intervillous space (IVS). Even after treatment, past PM (presence of hemozoin crystals from the parasite in the placenta) can cause a chronic inflammatory response. We predicted that the activation states of the maternal monocytes and fetal macrophages differ within the placenta and respond according to the parasite burden (active vs. past PM). We studied formalin-fixed paraffin-embedded placental biopsies from PM and healthy pregnancies. RNAscope HiPlex v2 in situ-hybridization technique was used to characterize the phenotypes of CD68 (pan-monocyte/macrophage marker), CD163 (anti-inflammatory macrophage marker), FOLR2 [tissue resident macrophage marker- fetal Hofbauer cells (HBCs)], and KRT7 (trophoblast marker). In the IVS compartment, the densities of pro-inflammatory maternal macrophages (FOLR2-CD163-), anti-inflammatory maternal macrophages (FOLR2-CD163+) and anti-inflammatory fetal HBCs (FOLR2+CD163+) showed a 3-, 3-, and 4-fold increase, respectively, in active PM compared to past PM (p< 0.05). In the placental villi, the density of pro-inflammatory maternal macrophages (FOLR2 CD163-) demonstrated a 5-fold increase in past PM compared to active PM (p< 0.05). The results demonstrate in active PM, anti-inflammatory fetal HBCs transmigrate into the IVS, recruiting both anti- and pro-inflammatory maternal macrophages. These results contribute to the understanding of the pathophysiology of PM and the development of treatments to diminish the effects of past PM.

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