PMID- 16611373
OWN - NLM
STAT- MEDLINE
DCOM- 20080401
LR  - 20211020
IS  - 1475-4924 (Electronic)
IS  - 1478-5854 (Print)
IS  - 1475-4924 (Linking)
VI  - 5
IP  - 2
DP  - 2006
TI  - Suppression of adaptive immunity to heterologous antigens during Plasmodium 
      infection through hemozoin-induced failure of dendritic cell function.
PG  - 5
AB  - BACKGROUND: Dendritic cells (DCs) are central to the initiation and regulation of 
      the adaptive immune response during infection. Modulation of DC function may 
      therefore allow evasion of the immune system by pathogens. Significant depression 
      of the host's systemic immune response to both concurrent infections and 
      heterologous vaccines has been observed during malaria infection, but the 
      mechanisms underlying this immune hyporesponsiveness are controversial. RESULTS: 
      Here, we demonstrate that the blood stages of malaria infection induce a failure 
      of DC function in vitro and in vivo, causing suboptimal activation of T cells 
      involved in heterologous immune responses. This effect on T-cell activation can 
      be transferred to uninfected recipients by DCs isolated from infected mice. 
      Significantly, T cells activated by these DCs subsequently lack effector 
      function, as demonstrated by a failure to migrate to lymphoid-organ follicles, 
      resulting in an absence of B-cell responses to heterologous antigens. 
      Fractionation studies show that hemozoin, rather than infected erythrocyte (red 
      blood cell) membranes, reproduces the effect of intact infected red blood cells 
      on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas 
      of the spleen in vivo. CONCLUSION: Plasmodium infection inhibits the induction of 
      adaptive immunity to heterologous antigens by modulating DC function, providing a 
      potential explanation for epidemiological studies linking endemic malaria with 
      secondary infections and reduced vaccine efficacy.
FAU - Millington, Owain R
AU  - Millington OR
AD  - Division of Immunology, Infection and Inflammation, University of Glasgow, 
      Glasgow G11 6NT, UK. owain.millington@strath.ac.uk
FAU - Di Lorenzo, Caterina
AU  - Di Lorenzo C
FAU - Phillips, R Stephen
AU  - Phillips RS
FAU - Garside, Paul
AU  - Garside P
FAU - Brewer, James M
AU  - Brewer JM
LA  - eng
GR  - 066890/Z/02/Z/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20060412
PL  - England
TA  - J Biol
JT  - Journal of biology
JID - 101147570
RN  - 0 (Antigens, Protozoan)
RN  - 0 (Hemeproteins)
RN  - 39404-00-7 (hemozoin)
SB  - IM
CIN - J Biol. 2006;5(2):4. PMID: 16620370
MH  - Animals
MH  - Antigens, Protozoan/immunology
MH  - B-Lymphocytes/immunology/parasitology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Erythrocytes/immunology/parasitology
MH  - Female
MH  - Hemeproteins/*immunology
MH  - *Immune Tolerance
MH  - Malaria/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Plasmodium/*immunology
MH  - Spleen/immunology
MH  - T-Lymphocytes/immunology/parasitology
PMC - PMC1561486
EDAT- 2006/04/14 09:00
MHDA- 2008/04/02 09:00
PMCR- 2006/04/12
CRDT- 2006/04/14 09:00
PHST- 2005/09/02 00:00 [received]
PHST- 2005/12/16 00:00 [revised]
PHST- 2006/03/02 00:00 [accepted]
PHST- 2006/04/14 09:00 [pubmed]
PHST- 2008/04/02 09:00 [medline]
PHST- 2006/04/14 09:00 [entrez]
PHST- 2006/04/12 00:00 [pmc-release]
AID - jbiol34 [pii]
AID - 10.1186/jbiol34 [doi]
PST - ppublish
SO  - J Biol. 2006;5(2):5. doi: 10.1186/jbiol34. Epub 2006 Apr 12.