title: Low-level Plasmodium falciparum blood-stage infection causes dendritic cell apoptosis and dysfunction in healthy volunteers.
abstract: BACKGROUND
  Dendritic cells (DCs) are highly specialized antigen-presenting cells that are crucial for initiation of immune responses. During naturally acquired malaria, DC number and function is reduced.
  
  
  METHODS
  The timing of, parasitemia threshold of, and contribution of apoptosis to DC loss were prospectively evaluated in 10 men after experimental challenge with approximately 1800 Plasmodium falciparum-parasitized red blood cells (pRBCs) and after drug cure initiated at a parasite level of ≥ 1000 parasites/mL.
  
  
  RESULTS
  The nadir levels of total, myeloid, and plasmacytoid DCs occurred 8 days after infection. DC loss was partially attributable to apoptosis, which was first detected on day 5 (median parasite level, 238 parasites/mL) and maximal at day 7. Remaining DCs exhibited a reduced ability to uptake particulate antigen. DC numbers recovered approximately 60 hours after antimalarial drug administration. There was no loss of DC number or function before or after drug cure in 5 men inoculated with <180 pRBCs and treated on day 6, when their parasite level was approximately 200 parasites/mL.
  
  
  CONCLUSIONS
  Plasmodium causes DC loss in vivo, which is at least partially explained by apoptosis in response to blood-stage parasites. In primary infection, loss of DC number and function occurs early during the prepatent period and before or with onset of clinical symptoms. These findings may explain in part the inadequate development of immunity to blood-stage malaria infection.
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia. tonia.woodberry@menzies.edu.au
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Gabriela
authors.initials: G
authors.lastname: Minigo
authors.forename: Kim A
authors.initials: KA
authors.lastname: Piera
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Amante
authors.forename: Alberto
authors.initials: A
authors.lastname: Pinzon-Charry
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
authors.forename: J Alejandro
authors.initials: JA
authors.lastname: Lopez
authors.forename: Christian R
authors.initials: CR
authors.lastname: Engwerda
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003713:Dendritic Cells / Q000473:pathology* / Q000502:physiology*; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use; D005449:Fluorenes / Q000627:therapeutic use; D005786:Gene Expression Regulation; D006801:Humans; D018655:Lymphocyte Count; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000502:physiology; D018512:Parasitemia / Q000473:pathology; D010963:Plasmodium falciparum / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D016207:Cytokines; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes