Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Abstract

Upon transmission to the human host, Plasmodium sporozoites exit the skin, are taken up by the blood stream, and then travel to the liver where they infect and significantly modify a single hepatocyte. Low infection rates within the liver have made proteomic studies of infected hepatocytes challenging, particularly in vivo, and existing studies have been largely unable to consider how protein and phosphoprotein differences are altered at different spatial locations within the heterogeneous liver. Using digital spatial profiling, we characterized changes in host signaling during Plasmodium yoelii infection in vivo without disrupting the liver tissue. Moreover, we measured alterations in protein expression around infected hepatocytes and identified a subset of CD163+ Kupffer cells that migrate towards infected cells during infection. These data offer the first insight into the heterogeneous microenvironment that surrounds the infected hepatocyte and provide insights into how the parasite may alter its milieu to influence its survival and modulate immunity.

The Utility of Spatial Transcriptomics for Solid Organ Transplantation

“…These ROIs are then exposed to ultraviolet light to cleave the oligo probes that are collected and quantified on a custom nCounter analysis system or genomic sequencer. In this manner, ISH-based ST has allowed the visualization of tissue niches of interest in complex tissue sections such as brain [36][37][38] and liver 39 by MERFISH and kidney, 40,41 colon, 42 liver, 43 and lung 44 by GeoMx DSP. Based on the number of probes and size of tissue or ROI, both ISH-based ST techniques are simple, cost-effective, and high-throughput relative to ISS-based ST.…”