infantum[14], have been reported previously to down-regulate CD1a expression. L. donovani was also shown to prevent activation of CD1-restricted T cells by DCs, which may represent a survival strategy by avoiding parasite glycolipid recognition [12]. L. amazonensis https://www.selleckchem.com/products/mitomycin-c.html was able to alter DC differentiation by inducing a significant decrease in CD1a and CD80 expression and a significant increase in CD86 expression, causing down-regulation of the Th1 adaptive immune response [16]. We did not observe significant down-regulation of CD80 or increase of CD86. This could
be attributed to differences in the biology of Lm and L. amazonensis. In the last part of our work we showed that, despite their intracellular location, Lm clones did not stimulate IL-12p70, TNF-α or IL-10
production by DCs. In agreement with our results, others have reported that the uptake of the parasites alone by immature DCs provided an insufficient stimulus for cytokine production [6,11–13,25]. However, in the presence of an appropriate co-stimulation, and depending on the life stage and species involved, Leishmania parasites were shown to be able to modulate cytokine production by human DCs. We showed that, independently of their virulence, Lm clones were able to induce a decrease of IL-12p70 secretion during LPS-induced maturation of DC. Interestingly, although the LV Lm clone www.selleckchem.com/products/poziotinib-hm781-36b.html was not internalized by DCs, it was able to down-regulate IL-12p70 production during DC maturation similarly to the high virulent clone. It has been suggested that Leishmania-induced maturation does not require infection of DC and that direct recognition of parasites by DCs could be sufficient [28]. In agreement with our data, altered DC responsiveness to exogenous stimuli in the presence of Leishmania parasites and antigens has been reported by others [12,16,25]. L. donovani parasites crotamiton and
excreted–secreted antigens from L. donovani and Lm inhibited strongly IL-12p70 secretion by mature DCs [25]. Leishmania phosphoglycans family of virulence-associated antigens were able to inhibit DC maturation [29]. Conversely, it was reported that Lm was able to prime DC for CD40L-dependent IL-12p70 production [6,11,30] in a life stage and species- and strain-dependent manner [11]. This variability of Leishmania parasites ability to modulate a human DCs cytokine response could be explained not only by intrinsic differences between Leishmania species or strains or infective stage, but also by differences in the specific culture conditions such as the nature of priming and triggering signals used to induce maturation.