This protein is expressed predominantly at both the mRNA and prot

This protein is expressed predominantly at both the mRNA and protein levels in highly virulent strains. Moreover, its enzymatic activity is altered by specific PDI inhibitors which profoundly affect parasite growth [20]. Furthermore, Ben Achour et al. showed

that Lm parasites deleted for APO866 in vivo the lmpdi gene are non-virulent in experimental leishmaniasis induced in BALB/c mice (unpublished data). However, unexpectedly, our results indicated that in LV clones, the lmpdi gene deletion, although having no effect on parasite burden, was associated with an increase of the infection rate. These unexpected results could be attributed to the fact that virulence of Lm clones as well as lmpdi-deleted clones was established in mice. It is well known that relating results observed in experimental murine leishmaniasis to humans is not always obvious. Alternatively, a decrease in virulence of lmpdi-deleted parasites in the human host, as shown in mice, cannot be excluded, as several factors involved in in-vivo Leishmania-DCs interactions are absent in in-vitro experiments. Conversely, we cannot exclude that differential expression of the lmpdi gene between HV and LV parasites could be associated with a differential role on human DC infectivity. Overall, our results suggest

that there is a correlation between virulence of Lm clones and ability to infect and to replicate in human myeloid learn more DCs. Moreover, LmPDI protein may be associated with DC infectivity. Due to its key role in assisting Leishmania protein folding via its capacity to catalyse formation, breakage and rearrangement of disulphide bonds in nascent polypeptides [20,24], LmPDI could be implicated either directly or indirectly in attachment, internalization or intracellular multiplication of Lm parasites.

Contradictory data are reported concerning the in-vitro infectivity of human DCs by Leishmania parasites. Comparable levels of parasite uptake by human DCs were reported MycoClean Mycoplasma Removal Kit for Lm, L. tropica and L. donovani promastigotes [11], whereas other authors showed lower infectivity for two virulent L. donovani strains [13]. These results could be explained in part by variability in the virulence of the Leishmania strains. Our results are in agreement with those of previous studies on the capacity of Lm to infect human DCs [6,11,25]. However, to our knowledge, this is the first demonstration of a significant difference in the in-vitro infectivity of human DCs by Lm strains differing by their virulence. Recently, it was reported that DCs control the intracellular growth of mycobacteria strains differently, suggesting variability in the cell-to-cell spread outcome during the first step of infection [26]. The second goal of this study was to analyse the impact of Lm virulence on DC differentiation. Our data showed that Lm clones were able to alter DC differentiation by down-regulating CD1a expression, whatever their virulence. L.

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