PMID- 17785836
OWN - NLM
STAT- MEDLINE
DCOM- 20071105
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 179
IP  - 6
DP  - 2007 Sep 15
TI  - Systemic tumor necrosis factor generated during lethal Plasmodium infections 
      impairs dendritic cell function.
PG  - 3982-7
AB  - Dendritic cells (DCs) initiate innate and adaptive immune responses including 
      those against malaria. Although several studies have shown that DC function is 
      normal during malaria, other studies have shown compromised function. To 
      establish why these studies had different findings, we examined DCs from mice 
      infected with two lethal species of parasite, Plasmodium berghei or P. vinckei, 
      and compared them to DCs from nonlethal P. yoelii 17XNL or P. chabaudi 
      infections. These studies found that DCs from only the lethal infections became 
      uniformly mature 7 days after infection and were functionally impaired as they 
      were unable to endocytose latex particles, secrete IL-12, or present OVA to 
      transgenic OTII T cells. These changes coincided with a peak in levels of 
      systemic TNF-alpha. Because TNF-alpha is known to mature DCs, we used TNF-KO mice 
      to determine the role of this cytokine in the loss of DC function. In the TNF-KO 
      mice, phenotype, Ag presentation, and IL-12 secretion by DCs were restored to 
      normal following both lethal infections. This study shows that the systemic 
      production of TNF-alpha contributes to poor DC function during lethal infections. 
      These studies may explain, at least in part, immunosuppression that is associated 
      with malaria.
FAU - Wykes, Michelle N
AU  - Wykes MN
AD  - The Molecular Immunology Laboratory, The Queensland Institute of Medical 
      Research, The Bancroft Centre, Brisbane, Queensland, Australia.
FAU - Liu, Xue Q
AU  - Liu XQ
FAU - Jiang, Suhua
AU  - Jiang S
FAU - Hirunpetcharat, Chakrit
AU  - Hirunpetcharat C
FAU - Good, Michael F
AU  - Good MF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antigen Presentation/immunology
MH  - Antigens/metabolism
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/*immunology/*metabolism/pathology
MH  - Endocytosis/immunology
MH  - Female
MH  - Immune Tolerance/genetics
MH  - Malaria/genetics/*immunology/mortality/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Plasmodium berghei/immunology
MH  - Plasmodium chabaudi/immunology
MH  - Plasmodium yoelii/immunology
MH  - Spleen/cytology/immunology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/*blood/deficiency/genetics
EDAT- 2007/09/06 09:00
MHDA- 2007/11/06 09:00
CRDT- 2007/09/06 09:00
PHST- 2007/09/06 09:00 [pubmed]
PHST- 2007/11/06 09:00 [medline]
PHST- 2007/09/06 09:00 [entrez]
AID - 179/6/3982 [pii]
AID - 10.4049/jimmunol.179.6.3982 [doi]
PST - ppublish
SO  - J Immunol. 2007 Sep 15;179(6):3982-7. doi: 10.4049/jimmunol.179.6.3982.