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Table 3 Gene expression studies informing understanding of naturally acquired immunity to malaria infection

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

Measure of NAIPublicationDesignSampleSpeciesSubjects for comparisonKey findingComment
Prior exposure to malariaTran et al. (2016)Comparison of GEP changes from paired infected and uninfected samplesWhole bloodP. falciparumMalaria-naïve, symptomatic Dutch CHMI volunteers at diagnosis (n = 5)Malaria experienced Malian children (> 13 years) and adults infected in the field (n = 8)Graded activation of pathways of downstream proinflammatory cytokines with highest activation in malaria-naive subjects and significantly reduced activation in malaria experienced Malians 
Ockenhouse et al. (2006)Comparison of GEP changes in infection-controls samples US malaria naïve subjectsPBMCP. falciparumUS malaria-naïve CHMI volunteers with early, blood-stage infection (n = 22)Malaria-experienced Cameroonian adults presenting with naturally acquired febrile malaria (n = 15)Similar induction of pro-inflammatory cytokines seen between pre-symptomatic and symptomatic individuals regardless of prior malaria exposure 
Rojas-Pena et al. (2015) and Vallejo et al. (2018)Comparison of GEP changes from paired infected and uninfected samplesWhole bloodP. vivaxColumbian malaria-naïve (MN) CHMI volunteers at diagnosis (n = 7)Columbian malaria-exposed (ME) CHMI volunteers at diagnosis (n = 9)Little differentiation seen between MN and ME populations by Rojas-Penas et al. However network co-expression analysis by Vallejo et al. showed the inflammatory response was attenuated in ME volunteers with decreased class II antigen presentation in dendritic cellsNo significant difference between groups for pre-patent period or parasitaemia at diagnosis suggesting there may have been no difference in functional immunity between groups
Jagannathan et al. (2014)Comparison of GEP between groupsVδ2+ T cellsP. falciparumUgandan children with low prior malaria incidence (n = 4)Ugandan children with low prior malaria incidence (n = 4)Comparison of basal gene expression patterns of sorted, un-stimulated Vδ2+ T cells identified 48 differentially expressed genes, many with known roles in immunomodulation. For each of these genes, expression was higher among children with high prior exposure to malariaData suggest recurrent malaria infection causes up-regulation of immunoregulatory pathways that dampen the pro-inflammatory immune response to P. falciparum infection and help explain immunological tolerance to the parasite
Symptoms at diagnosisTran et al. (2016)Comparison of GEP changes from paired infected and uninfected samplesWhole bloodP. falciparumMalaria experienced Malian children (> 13 years) and adults infected in the field and asymptomatic at diagnosis (EA, n = 5)Malaria experienced Malian children (> 13 years) and adults infected in the field and symptomatic with fever at the time of diagnosis (EF, n = 3)Only 70 differentially expressed genes (DEGs) were identified between these groups despite the apparent clinical differences2 of the 5 individuals in the EA group progressed to febrile malaria within 5 days of initial diagnosis by PCR
Disease severityKrupka et al. (2012)Comparison of GEP in same subjects at diagnosis with severe and subsequent mild malariaWhole bloodP. falciparumMalawian children who, after presenting with severe malaria (all had cerebral malaria), were found to have mild malaria one month later on screening by blood smear (n = 5)Pathway analysis showed relative up regulation of Type I IFN signaling pathway, regulation of inflammation, regulation of leukocyte proliferation and T cell activation in episodes of mild malaria 
Boldt et al. (2019)Comparison of GEP between groupsWhole bloodP. falciparumHealthy uninfected Gabonese childrenGabonese children with asymptomatic parasitaemia, mild malaria, malaria with severe anaemia and cerebral anaemia (0.5–6 years)GEP of 22 genes significantly differed among groups. Immunoglobulin production, complement regulation and IFN beta signaling were most conspicuous 
  1. PBMC peripheral blood mononuclear cells, GEP gene expression profile, CHMI controlled human malaria infection