Cytoadhesion of Plasmodium Falciparum-Infected Red Blood Cells Changes the Expression of Cytokine-, Histone- and Antiviral Protein-Encoding Genes in Brain Endothelial Cells

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2024 Dec 4

PMID 39630601

Authors

Johannes Allweier

Michael Bartels

Hanifeh Torabi

Maria Del Pilar Martinez Tauler

Nahla Galal Metwally

Thomas Roeder

Thomas Gutsmann

Iris Bruchhaus

Affiliations

Soon will be listed here.

Abstract

Malaria remains a significant global health problem, mainly due to Plasmodium falciparum, which is responsible for most fatal infections. Infected red blood cells (iRBCs) evade spleen clearance by adhering to endothelial cells (ECs), triggering capillary blockage, inflammation, endothelial dysfunction and altered vascular permeability, prompting an endothelial transcriptional response. The iRBC/HBEC-5i model, where iRBCs present IT4var04 (VAR2CSA) on their surface, was used to analyze the effects of iRBC binding on ECs at different temperature (37°C vs. 40°C). Binding of non-infected RBCs (niRBCs) and fever alone altered the expression of hundreds of genes in ECs. Comparing the expression profile of HBEC-5i cells cultured either in the presence of iRBCs or in the presence of niRBCs revealed significant upregulation of genes linked to immune response, nucleosome assembly, NF-kappa B signaling, angiogenesis, and antiviral immune response/interferon-alpha/beta signaling. Raising the temperature to 40°C, simulating fever, led to further upregulation of many genes, particularly those involved in cytokine production and angiogenesis. In summary, the presence of iRBCs stimulates ECs, activating several immunological pathways and affecting antiviral (-parasitic) mechanisms and angiogenesis. Our data uncovered the induction of the interferon-alpha/beta signaling pathway in ECs in response to iRBCs.

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