PMID- 22615323
OWN - NLM
STAT- MEDLINE
DCOM- 20120925
LR  - 20181201
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 206
IP  - 3
DP  - 2012 Aug 1
TI  - Low-level Plasmodium falciparum blood-stage infection causes dendritic cell 
      apoptosis and dysfunction in healthy volunteers.
PG  - 333-40
LID - 10.1093/infdis/jis366 [doi]
AB  - 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.
FAU - Woodberry, Tonia
AU  - Woodberry T
AD  - Global and Tropical Health Division, Menzies School of Health Research, Charles 
      Darwin University, Darwin, Northern Territory, Australia. 
      tonia.woodberry@menzies.edu.au
FAU - Minigo, Gabriela
AU  - Minigo G
FAU - Piera, Kim A
AU  - Piera KA
FAU - Amante, Fiona H
AU  - Amante FH
FAU - Pinzon-Charry, Alberto
AU  - Pinzon-Charry A
FAU - Good, Michael F
AU  - Good MF
FAU - Lopez, J Alejandro
AU  - Lopez JA
FAU - Engwerda, Christian R
AU  - Engwerda CR
FAU - McCarthy, James S
AU  - McCarthy JS
FAU - Anstey, Nicholas M
AU  - Anstey NM
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120521
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Antimalarials)
RN  - 0 (Artemether, Lumefantrine Drug Combination)
RN  - 0 (Artemisinins)
RN  - 0 (Cytokines)
RN  - 0 (Drug Combinations)
RN  - 0 (Ethanolamines)
RN  - 0 (Fluorenes)
SB  - IM
MH  - Adult
MH  - Antimalarials/therapeutic use
MH  - Apoptosis/*physiology
MH  - Artemether, Lumefantrine Drug Combination
MH  - Artemisinins/therapeutic use
MH  - Cytokines/blood/genetics
MH  - Dendritic Cells/*pathology/*physiology
MH  - Drug Combinations
MH  - Ethanolamines/therapeutic use
MH  - Fluorenes/therapeutic use
MH  - Gene Expression Regulation
MH  - Humans
MH  - Lymphocyte Count
MH  - Malaria, Falciparum/drug therapy/*pathology
MH  - Male
MH  - Monocytes/physiology
MH  - Parasitemia/pathology
MH  - Plasmodium falciparum/*physiology
MH  - Polymerase Chain Reaction
MH  - Prospective Studies
MH  - Time Factors
MH  - Young Adult
EDAT- 2012/05/23 06:00
MHDA- 2012/09/26 06:00
CRDT- 2012/05/23 06:00
PHST- 2012/05/23 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/09/26 06:00 [medline]
AID - jis366 [pii]
AID - 10.1093/infdis/jis366 [doi]
PST - ppublish
SO  - J Infect Dis. 2012 Aug 1;206(3):333-40. doi: 10.1093/infdis/jis366. Epub 2012 May 
      21.