PMID- 22659438
OWN - NLM
STAT- MEDLINE
DCOM- 20121109
LR  - 20200214
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 13
IP  - 4
DP  - 2012 Aug
TI  - Targeting Toll-like receptors by chloroquine protects mice from experimental 
      cerebral malaria.
PG  - 392-7
LID - 10.1016/j.intimp.2012.05.012 [doi]
AB  - Excessive production of proinflammatory cytokines, elicited mostly by Th1 cells, 
      is an important cause of cerebral malaria (CM). Dendritic cells (DCs), a critical 
      link between innate and adaptive immune responses, rely heavily on Toll-like 
      receptor (TLR) signaling. Using C57BL/6 mice infected with Plasmodium berghei 
      ANKA (PbA) as an experimental CM model, we first confirmed that inhibition of 
      TLR9 by suppressive oligodeoxynucleotides protected mice from CM. In addition to 
      being a well-known antimalarial, chloroquine (CQ) has been used as an 
      immunomodulator of endocytic TLRs because it inhibits endosomal acidification. We 
      found that immediately before and shortly after infection by PbA, treatment with 
      a single dose of 50 mg/kg of CQ protected mice from experimental CM. Both CQ 
      treatments significantly inhibited expression of TLR9 and MHC-II on DCs, and 
      reduced the number of myeloid and plasmatocytoid DCs at 3 and 5 days after 
      infection. Consequently, activation of CD4+ T cells, especially the expansion of 
      the Th1 subsets, was dramatically inhibited in CQ treated groups, which was 
      accompanied by a remarkable decline in the production of Th1 type proinflammatory 
      mediators IFN-gamma, TNF-alpha, and nitric oxide. Taken together, these results 
      corroborated the involvement of TLR9 in CM pathogenesis and suggest that 
      interference with the activation of this receptor is a promising strategy to 
      prevent deleterious inflammatory response mediating pathogenesis and severity of 
      malaria.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Zhu, Xiaotong
AU  - Zhu X
AD  - Department of Immunology, College of Basic Medical Sciences, China Medical 
      University, Shenyang, Liaoning, China.
FAU - Pan, Yanyan
AU  - Pan Y
FAU - Li, Ying
AU  - Li Y
FAU - Jiang, Yongjun
AU  - Jiang Y
FAU - Shang, Hong
AU  - Shang H
FAU - Gowda, D Channe
AU  - Gowda DC
FAU - Cui, Liwang
AU  - Cui L
FAU - Cao, Yaming
AU  - Cao Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120601
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antimalarials)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Oligoribonucleotides, Antisense)
RN  - 0 (Toll-Like Receptor 9)
RN  - 886U3H6UFF (Chloroquine)
SB  - IM
MH  - Animals
MH  - Antimalarials/*administration & dosage/adverse effects
MH  - Cells, Cultured
MH  - Chloroquine/*administration & dosage/adverse effects
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*drug effects/immunology/parasitology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/immunology
MH  - Histocompatibility Antigens Class II/genetics/metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Malaria, Cerebral/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Targeted Therapy
MH  - Oligoribonucleotides, Antisense/genetics
MH  - Plasmodium berghei/*immunology
MH  - Th1 Cells/immunology
MH  - Toll-Like Receptor 9/genetics/*metabolism
EDAT- 2012/06/05 06:00
MHDA- 2012/11/10 06:00
CRDT- 2012/06/05 06:00
PHST- 2011/12/21 00:00 [received]
PHST- 2012/05/15 00:00 [revised]
PHST- 2012/05/21 00:00 [accepted]
PHST- 2012/06/05 06:00 [entrez]
PHST- 2012/06/05 06:00 [pubmed]
PHST- 2012/11/10 06:00 [medline]
AID - S1567-5769(12)00150-6 [pii]
AID - 10.1016/j.intimp.2012.05.012 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2012 Aug;13(4):392-7. doi: 10.1016/j.intimp.2012.05.012. 
      Epub 2012 Jun 1.