PMID- 20231693
OWN - NLM
STAT- MEDLINE
DCOM- 20100527
LR  - 20181113
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 8
DP  - 2010 Apr 15
TI  - Protein-DNA complex is the exclusive malaria parasite component that activates 
      dendritic cells and triggers innate immune responses.
PG  - 4338-48
LID - 10.4049/jimmunol.0903824 [doi]
AB  - Dendritic cells (DCs) play a crucial role in the development of protective 
      immunity to malaria. However, it remains unclear how malaria parasites trigger 
      immune responses in DCs. In this study, we purified merozoites, food vacuoles, 
      and parasite membrane fragments released during the Plasmodium falciparum 
      schizont burst to homogeneity and tested for the activation of bone 
      marrow-derived DCs from wild-type and TLR2(-/-), TLR4(-/-), TLR9(-/-), and 
      MyD88(-/-) C57BL/6J mice. The results demonstrate that a protein-DNA complex is 
      the exclusive parasite component that activates DCs by a TLR9-dependent pathway 
      to produce inflammatory cytokines. Complex formation with proteins is essential 
      for the entry of parasite DNA into DCs for TLR9 recognition and, thus, proteins 
      convert inactive DNA into a potent immunostimulatory molecule. Exogenous cationic 
      polymers, polylysine and chitosan, can impart stimulatory activity to parasite 
      DNA, indicating that complex formation involves ionic interactions. Merozoites 
      and DNA-protein complex could also induce inflammatory cytokine responses in 
      human blood DCs. Hemozoin is neither a TLR9 ligand for DCs nor functions as a 
      carrier of DNA into cells. Additionally, although TLR9 is critical for DCs to 
      induce the production of IFN-gamma by NK cells, this receptor is not required for 
      NK cells to secret IFN-gamma, and cell-cell contact among myeloid DCs, 
      plasmacytoid DCs, and NK cells is required for IFN-gamma production. Together, 
      these results contribute substantially toward the understanding of malaria 
      parasite-recognition mechanisms. More importantly, our finding that proteins and 
      carbohydrate polymers are able to confer stimulatory activity to an otherwise 
      inactive parasite DNA have important implications for the development of a 
      vaccine against malaria.
FAU - Wu, Xianzhu
AU  - Wu X
AD  - Department of Biochemistry and Molecular Biology, Pennsylvania State University 
      College of Medicine, Hershey, PA 17033, USA.
FAU - Gowda, Nagaraj M
AU  - Gowda NM
FAU - Kumar, Sanjeev
AU  - Kumar S
FAU - Gowda, D Channe
AU  - Gowda DC
LA  - eng
GR  - R01 AI041139/AI/NIAID NIH HHS/United States
GR  - R01 AI041139-12/AI/NIAID NIH HHS/United States
GR  - AI 41139/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100315
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA, Protozoan)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
CIN - Future Microbiol. 2010 Aug;5(8):1167-71. PMID: 20722596
MH  - Animals
MH  - Cell Communication/immunology
MH  - Cell Line
MH  - DNA, Protozoan/blood/*physiology
MH  - Dendritic Cells/*immunology/metabolism/*parasitology
MH  - Humans
MH  - *Immunity, Innate
MH  - Interferon-gamma/biosynthesis
MH  - Killer Cells, Natural/immunology/metabolism/parasitology
MH  - Malaria Vaccines/immunology
MH  - Malaria, Falciparum/blood/immunology/parasitology
MH  - Merozoites/growth & development/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Plasmodium falciparum/growth & development/*immunology
MH  - Protozoan Proteins/blood/*physiology
MH  - Toll-Like Receptor 9/blood/deficiency/genetics
PMC - PMC2851449
MID - NIHMS186059
EDAT- 2010/03/17 06:00
MHDA- 2010/05/28 06:00
PMCR- 2011/04/15
CRDT- 2010/03/17 06:00
PHST- 2010/03/17 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/05/28 06:00 [medline]
PHST- 2011/04/15 00:00 [pmc-release]
AID - jimmunol.0903824 [pii]
AID - 10.4049/jimmunol.0903824 [doi]
PST - ppublish
SO  - J Immunol. 2010 Apr 15;184(8):4338-48. doi: 10.4049/jimmunol.0903824. Epub 2010 
      Mar 15.