title: Circulating concentrations of soluble granzyme A and B increase during natural and experimental Plasmodium falciparum infections.
abstract: Release of soluble Granzymes (sGranzymes) is considered to reflect activation of cytotoxic T lymphocytes and NK cells. sGranzymes and a number of pro-inflammatory cytokines were measured in plasma of malaria patients with natural or experimentally induced Plasmodium falciparum infections. Concentrations of sGranzyme A and B, IL-10, IL-12p70 and CRP were significantly increased in African children presenting with clinical malaria; IL-10 and CRP concentrations were significantly correlated with disease severity. In nonimmune Dutch volunteers which were experimentally infected by P. falciparum-infected mosquitoes, sGranzyme A increment started 1-2 days prior to clinical symptoms and microscopically detectable parasitaemia. This coincided with increases in IFNgamma, IL-12p40 and IL-8, while sGranzyme B and IL-10 levels increased 24-48 h later. The elevation of sGranzyme A and IFNgamma in nonimmune volunteers suggests that NK cells are activated upon release of parasites by infected liver cells and subsequently during blood stage infection; thus, NK cells are likely involved innate immune human host resistance in the early phase of a malaria infection.
authors.affiliation: Department of Medical Microbiology, University Medical Center, Nijmegen, The Netherlands. r.hermsen@ncmls.kun.nl
authors.forename: C C
authors.initials: CC
authors.lastname: Hermsen
authors.forename: Y
authors.initials: Y
authors.lastname: Konijnenberg
authors.forename: L
authors.initials: L
authors.lastname: Mulder
authors.forename: C
authors.initials: C
authors.lastname: Loé
authors.forename: M
authors.initials: M
authors.lastname: van Deuren
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: G J
authors.initials: GJ
authors.lastname: van Mierlo
authors.forename: W M C
authors.initials: WM
authors.lastname: Eling
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: R W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000293:Adolescent; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D053804:Granzymes; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology; D016778:Malaria, Falciparum / Q000201:enzymology* / Q000276:immunology; D018512:Parasitemia / Q000201:enzymology / Q000276:immunology; D012697:Serine Endopeptidases / Q000097:blood*; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D002097:C-Reactive Protein; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human