Document Detail

Plasmodium yoelii sporozoites modulate cytokine profile and induce apoptosis in murine Kupffer cells.
MedLine Citation:
PMID:  18656478     Owner:  NLM     Status:  MEDLINE    
Plasmodium sporozoites traverse Kupffer cells on their way into the liver. Sporozoite contact does not elicit a respiratory burst in these hepatic macrophages and blocks the formation of reactive oxygen species in response to secondary stimuli via elevation of the intracellular cAMP concentration. Here we show that increasing the cAMP level with dibutyryl cyclic adenosine monophosphate (db-cAMP) or isobutylmethylxanthine (IBMX) also modulates cytokine secretion in murine Kupffer cells towards an overall anti-inflammatory profile. Stimulation of Plasmodium yoelii sporozoite-exposed Kupffer cells with lipopolysaccharide or IFN-gamma reveals down-modulation of TNF-alpha, IL-6 and MCP-1, and up-regulation of IL-10. Prerequisite for this shift of the cytokine profile are parasite viability and contact with Kupffer cells, but not invasion. Whilst sporozoite-exposed Kupffer cells become TUNEL-positive and exhibit other signs of apoptotic death such as membrane blebbing, nuclear condensation and fragmentation, sporozoites remain intact and appear to transform to early exo-erythrocytic forms in Kupffer cell cultures. Together, the in vitro data indicate that Plasmodium possesses mechanisms to render Kupffer cells insensitive to pro-inflammatory stimuli and eventually eliminates these macrophages by forcing them into programmed cell death.
Christian Klotz; Ute Frevert
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  International journal for parasitology     Volume:  38     ISSN:  1879-0135     ISO Abbreviation:  Int. J. Parasitol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2009-08-05     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0314024     Medline TA:  Int J Parasitol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1639-50     Citation Subset:  IM    
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MeSH Terms
1-Methyl-3-isobutylxanthine / metabolism
Apoptosis / immunology*
Bucladesine / metabolism
Cytokines / metabolism*
Host-Parasite Interactions
Interferon-gamma / pharmacology
Interleukins / metabolism
Kupffer Cells / drug effects,  immunology*
Lipopolysaccharides / pharmacology
Liver / metabolism,  pathology
Malaria / immunology*,  metabolism,  parasitology
Mice, Inbred BALB C
Plasmodium yoelii / immunology*
Sporozoites / physiology*
Tumor Necrosis Factor-alpha / metabolism
Grant Support
R01 AI051656/AI/NIAID NIH HHS; R01 AI051656-01/AI/NIAID NIH HHS; R01 AI051656-02/AI/NIAID NIH HHS; R01 AI051656-03/AI/NIAID NIH HHS; R01 AI051656-04/AI/NIAID NIH HHS; R01 AI051656-05/AI/NIAID NIH HHS; R01 AI51656/AI/NIAID NIH HHS; S10 RR019288/RR/NCRR NIH HHS; S10 RR019288/RR/NCRR NIH HHS; S10 RR019288-01/RR/NCRR NIH HHS; S10 RR019288-010001/RR/NCRR NIH HHS
Reg. No./Substance:
0/Cytokines; 0/Interleukins; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 63X7MBT2LQ/Bucladesine; 82115-62-6/Interferon-gamma; TBT296U68M/1-Methyl-3-isobutylxanthine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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