Document Detail

Effects of Leishmania major clones showing different levels of virulence on infectivity, differentiation and maturation of human dendritic cells.
MedLine Citation:
PMID:  22861367     Owner:  NLM     Status:  MEDLINE    
Leishmania parasites and dendritic cell interactions (DCs) play an essential role in initiating and directing T cell responses and influence disease evolution. These interactions may vary depending on Leishmania species and strains. To evaluate the correlation between Leishmania major (Lm) virulence and in-vitro human DC response, we compared the ability of high (HV) and low virulent (LV) Lm clones to invade, modulate cytokine production and interfere with differentiation of DCs. Clones derived from HV and LV (HVΔlmpdi and LVΔlmpdi), and deleted for the gene coding for a Lm protein disulphide isomerase (LmPDI), probably involved in parasite natural pathogenicity, were also used. Unlike LV, which fails to invade DCs in half the donors, HV promastigotes were associated with a significant increase of the infected cells percentage and parasite burden. A significant decrease of both parameters was observed in HVΔlmpdi-infected DCs, compared to wild-type cells. Whatever Lm virulence, DC differentiation was accompanied by a significant decrease in CD1a expression. Lm clones decreased interleukin (IL)-12p70 production similarly during lipopolysaccharide (LPS)-induced maturation of DCs. LPS stimulation was associated with a weak increase in tumour necrosis factor (TNF)-α and IL-10 productions in HV-, HVΔlmpdi- and LVΔlmpdi-infected DCs. These results indicate that there is a significant variability in the capacity of Lm clones to infect human DCs which depends upon their virulence, probably involving LmPDI protein. However, independently of their virulence, Lm clones were able to down-regulate CD1a expression during DC differentiation and IL-12p70 production during DC maturation, which may favour their survival.
W Markikou-Ouni; Y Ben Achour-Chenik; A Meddeb-Garnaoui
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  169     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-06     Completed Date:  2012-10-16     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  273-80     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Clinical and Experimental Immunology © 2012 British Society for Immunology.
Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Tunis, Tunisia.
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MeSH Terms
Antigens, CD1 / biosynthesis,  genetics
Cell Differentiation / drug effects,  immunology
Cells, Cultured / drug effects,  immunology
Clone Cells / immunology
Dendritic Cells / drug effects,  immunology*
Host-Pathogen Interactions / immunology
Interleukin-10 / biosynthesis,  genetics
Interleukin-12 / biosynthesis,  genetics
Leishmania major / genetics,  immunology*,  pathogenicity
Lipopolysaccharides / pharmacology
Protein Disulfide-Isomerases / deficiency
Protozoan Proteins / physiology
T-Lymphocyte Subsets / immunology
Tumor Necrosis Factor-alpha / biosynthesis,  genetics
Reg. No./Substance:
0/Antigens, CD1; 0/IL10 protein, human; 0/Lipopolysaccharides; 0/Protozoan Proteins; 0/Tumor Necrosis Factor-alpha; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; EC Disulfide-Isomerases

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