Abstract
Leishmania parasites and some molecules they secrete are known to modulate innate immune responses through effects on dendritic cells (DCs) and macrophages. Here, we characterized four Leishmania infantum potentially excreted/secreted recombinant proteins (LipESP) identified in our laboratory: Elongation Factor 1 alpha (LiEF-1α), a proteasome regulatory ATPase (LiAAA-ATPase) and two novel proteins with unknown functions, which we termed LiP15 and LiP23, by investigating their effect on in vitro differentiation and maturation of human DCs and on cytokine production by DCs and monocytes. During DCs differentiation, LipESP led to a significant decrease in CD1a. LiP23 and LiEF-1α, induced a decrease of HLA-DR and an increase of CD86 surface expression, respectively. During maturation, an up-regulation of HLA-DR and CD80 was found in response to LiP15, LiP23 and LiAAA-ATPase, while an increase of CD40 expression was only observed in response to LiP15. All LipESP induced an over-expression of CD86 with significant differences between proteins. These proteins also induced significant IL-12p70 levels in immature DCs but not in monocytes. The LipESP-induced IL-12p70 production was significantly enhanced by a co-treatment with IFN-γ in both cell populations. TNF-α and IL-10 were induced in DCs and monocytes with higher levels observed for LiP15 and LiAAA-ATPase. However, LPS-induced cytokine production during DC maturation or in monocyte cultures was significantly down regulated by LipESP co-treatment. Our findings suggest that LipESP strongly interfere with DCs differentiation suggesting a possible involvement in mechanisms established by the parasite for its survival. These proteins also induce DCs maturation by up-regulating several costimulatory molecules and by inducing the production of proinflammatory cytokines, which is a prerequisite for T cell activation. However, the reduced ability of LipESP-stimulated DCs and monocytes to respond to lipopolysaccharide (LPS) that can be observed during human leishmaniasis, suggests that under certain circumstances LipESP may play a role in disease progression.
Highlights
Leishmaniasis is a heterogeneous group of diseases caused by an intracellular protozoan parasite of the Leishmania genus, transmitted by a sandfly vector and associated with considerable morbidity and mortality throughout the world [1]
We examined the immunomodulatory effects of four potential L. infantum excreted/secreted proteins: LiEF-1α, LiAAA-ATPase, LiP15 and LiP23 on differentiation and maturation of two major phagocyte populations, dendritic cells (DCs) and monocytes playing critical roles during infection
We showed that HLA-DR expression was down regulated in LiP23-stimulated cells while CD86 expression was up regulated in LiEF-1α-stimulated cells, during DCs differentiation
Summary
Leishmaniasis is a heterogeneous group of diseases caused by an intracellular protozoan parasite of the Leishmania genus, transmitted by a sandfly vector and associated with considerable morbidity and mortality throughout the world [1]. To escape from the innate immune response, parasites have evolved subversion mechanisms that allow them to survive and grow inside phagocytic cells Among these mechanisms, the inhibition of protective cytokines production, interference with effective antigen presentation, or with host cell signaling events that lead to the generation of effectors molecules and activation/deactivation of DCs and macrophages functions by parasite factors [2, 3, 5,6,7]. We report a first characterization of LiEF-1α, LiAAA-ATPase, LiP15 and LiP23 based on the analysis of their immunomodulatory effects on in vitro differentiation and maturation of human DCs and on cytokine production by human DCs and monocytes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
