Characterizing the pathological events of human lung endothelial cells during P. falciparum infection

Abstract text

Characterizing the pathological events of human lung endothelial cells during P. falciparum infection

Hanifeh Torabi, Yifan Wu, Maria del Pilar Martinez Tauler, Barbara Honecker, Katharina Höhn, Iris Bruchhaus, Nahla Galal Metwally

Bernhard Nocht Institute for Tropical Medicine, RG Host Parasite Interaction, Hamburg, Germany

Introduction

Plasmodium falciparum is the main cause of morbidity and mortality in malaria patients, especially in children under five years of age. Understanding the pathogenesis of P. falciparum infection in the context of host-parasite interaction could lead to targets for adjunctive therapies. The sequestration of P. falciparum-infected erythrocytes (PfIEs) in the vascular bed of various organs, such as the brain, heart, lung, stomach, and kidney, allows the parasite to escape elimination by the spleen. Sequestration occurs due to an interaction between a parasite ligand presented on the surface of PfIEs and a number of human endothelial cell receptors (ECRs). This cytoadhesion is mainly attributed to members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, encoded by approximately 60 var genes per haploid parasite genome.

Objectives

Due to a bidirectional interaction between PfIEs and host ECRs, malaria infection can result in severe complications. These interactions likely vary from one tissue to another because of the differences in the ECR expression profiles. We hypothesize that these interactions do take place in the early phases of infection to alter the host's response once the parasite enters the bloodstream in order to survive. In addition, host cells interact with the PfIEs and most likely modify their biology. Some studies suggest that cytoadhesion does not provide the full explanation for the complications associated with malaria. In this context, extracellular vesicles (EVs) as cargo from cell to cell, carrying proteins and nucleic acids, are being investigated to gain a better understanding of the interaction between parasite and host. This study aimed to investigate the transcriptomes of lung ECs exposed to different stimuli occurring during P. falciparum infection in order to analyze the different profiles of tissue-specific PfIEs communication.

Results

We were able to enrich a parasite population that specifically binds to lung ECs. We are currently analyzing the transcriptomes of this parasite population. Furthermore, the miRNA profile of EVs secreted by lung ECs during P. falciparum infection is being determined.