Transcriptome-based analysis of blood samples reveals elevation of DNA damage response, neutrophil degranulation, cancer and neurodegenerative pathways in Plasmodium falciparum patients

• Published in: Malaria Journal
• Main Authors: Akua A. Karikari, Wasco Wruck, James Adjaye
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Cerebral malaria; P. falciparum; Cellular stress; Immune response; Neutrophil degranulation; Axonal dysfunction; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03918-5; https://doaj.org/article/d1e355388fb54995bbd4c434db2dc9ec

Abstract Background Malaria caused by Plasmodium falciparum results in severe complications including cerebral malaria (CM) especially in children. While the majority of falciparum malaria survivors make a full recovery, there are reports of some patients ending up with neurological sequelae or cognitive deficit. Methods An analysis of pooled transcriptome data of whole blood samples derived from two studies involving various P. falciparum infections, comprising mild malaria (MM), non-cerebral severe malaria (NCM) and CM was performed. Pathways and gene ontologies (GOs) elevated in the distinct P. falciparum infections were determined. Results In all, 2876 genes were expressed in common between the 3 forms of falciparum malaria, with CM having the least number of expressed genes. In contrast to other research findings, the analysis from this study showed MM share similar biological processes with cancer and neurodegenerative diseases, NCM is associated with drug resistance and glutathione metabolism and CM is correlated with endocannabinoid signalling and non-alcoholic fatty liver disease (NAFLD). GO revealed the terms biogenesis, DNA damage response and IL-10 production in MM, down-regulation of cytoskeletal organization and amyloid-beta clearance in NCM and aberrant signalling, neutrophil degranulation and gene repression in CM. Differential gene expression analysis between CM and NCM showed the up-regulation of neutrophil activation and response to herbicides, while regulation of axon diameter was down-regulated in CM. Conclusions Results from this study reveal that P. falciparum-mediated inflammatory and cellular stress mechanisms may impair brain function in MM, NCM and CM. However, the neurological deficits predominantly reported in CM cases could be attributed to the down-regulation of various genes involved in cellular function through transcriptional repression, axonal dysfunction, dysregulation of signalling pathways and neurodegeneration. It is anticipated that the data from this study, might form the ...