Use of gene expression studies to investigate the human immunological response to malaria infection

Abstract Background Transcriptional profiling of the human immune response to malaria has been used to identify diagnostic markers, understand the pathogenicity of severe disease and dissect the mechanisms of naturally acquired immunity (NAI). However, interpreting this body of work is difficult giv...

Full description

Bibliographic Details
Published in:Malaria Journal
Main Authors: Susanne H. Hodgson, Julius Muller, Helen E. Lockstone, Adrian V. S. Hill, Kevin Marsh, Simon J. Draper, Julian C. Knight
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2019
Subjects:
Online Access:https://doi.org/10.1186/s12936-019-3035-0
https://doaj.org/article/f055391fdd4b4f22a2a1afb06ebfb8af
Description
Summary:Abstract Background Transcriptional profiling of the human immune response to malaria has been used to identify diagnostic markers, understand the pathogenicity of severe disease and dissect the mechanisms of naturally acquired immunity (NAI). However, interpreting this body of work is difficult given considerable variation in study design, definition of disease, patient selection and methodology employed. This work details a comprehensive review of gene expression profiling (GEP) of the human immune response to malaria to determine how this technology has been applied to date, instances where this has advanced understanding of NAI and the extent of variability in methodology between studies to allow informed comparison of data and interpretation of results. Methods Datasets from the gene expression omnibus (GEO) including the search terms; ‘plasmodium’ or ‘malaria’ or ‘sporozoite’ or ‘merozoite’ or ‘gametocyte’ and ‘Homo sapiens’ were identified and publications analysed. Datasets of gene expression changes in relation to malaria vaccines were excluded. Results Twenty-three GEO datasets and 25 related publications were included in the final review. All datasets related to Plasmodium falciparum infection, except two that related to Plasmodium vivax infection. The majority of datasets included samples from individuals infected with malaria ‘naturally’ in the field (n = 13, 57%), however some related to controlled human malaria infection (CHMI) studies (n = 6, 26%), or cells stimulated with Plasmodium in vitro (n = 6, 26%). The majority of studies examined gene expression changes relating to the blood stage of the parasite. Significant heterogeneity between datasets was identified in terms of study design, sample type, platform used and method of analysis. Seven datasets specifically investigated transcriptional changes associated with NAI to malaria, with evidence supporting suppression of the innate pro-inflammatory response as an important mechanism for this in the majority of these studies. However, further ...