title: Asymptomatic plasmodial infection is associated with increased tumor necrosis factor receptor II-expressing regulatory T cells and suppressed type 2 immune responses.
abstract: BACKGROUND
  In malaria-endemic areas, a proportion of individuals becomes chronic carriers of parasites with few or no clinical signs. There is little information on cellular immune responses in asymptomatic parasite carriers.
  
  
  METHODS
  In 80 schoolchildren residing in a malaria-endemic area of Flores Island, Indonesia, T-helper subsets, regulatory T-cell (Treg) frequencies, tumor necrosis factor receptor type II (TNFRII) expression on Tregs, and cytokine responses induced by Plasmodium falciparum-infected red blood cells (RBCs) were measured, and values for asymptomatic infected subjects were compared to those for uninfected controls. To ascertain that alterations found were due to the presence of malaria parasites, the immune responses were analyzed in 16 children before and 1 month after antimalarial treatment.
  
  
  RESULTS
  TNFRII expression, a marker of activation on Tregs, was higher during infection but decreased upon treatment. GATA3-positive cells and the level of interleukin 13 secretion in response to P. falciparum-infected RBCs appeared to be suppressed by plasmodial infection, as both increased after antimalarial treatment. TNFRII expression on Tregs correlated positively with TNF in response to P. falciparum-infected RBCs, but this association disappeared following treatment.
  
  
  CONCLUSIONS
  Malaria parasites associated with asymptomatic infections seem to result in increased TNFRII expression on Tregs, as well as suppressed Th2 cytokine responses, features that might be important for survival of the parasites in asymptomatic carriers.
authors: Department of Parasitology, Leiden University Medical Center, the Netherlands.
authors: Linda J
authors: LJ
authors: Wammes
authors: Aprilianto E
authors: AE
authors: Wiria
authors: Christa G
authors: CG
authors: Toenhake
authors: Firdaus
authors: F
authors: Hamid
authors: Kit Yeng
authors: KY
authors: Liu
authors: Heni
authors: H
authors: Suryani
authors: Maria M M
authors: MM
authors: Kaisar
authors: Jaco J
authors: JJ
authors: Verweij
authors: Erliyani
authors: E
authors: Sartono
authors: Taniawati
authors: T
authors: Supali
authors: Hermelijn H
authors: HH
authors: Smits
authors: Adrian J
authors: AJ
authors: Luty
authors: Maria
authors: M
authors: Yazdanbakhsh
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000627:therapeutic use; D058345:Asymptomatic Infections; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007214:Indonesia; D018793:Interleukin-13 / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008297:Male; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000302:isolation & purification / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D015995:Prevalence; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells; D015854:Up-Regulation
chemical_list: D000962:Antimalarials; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018793:Interleukin-13; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human