Dendritic Cell Profile Induced bySchistosoma mansoniAntigen in Cutaneous Leishmaniasis Patients

Abstract

The inflammatory response in cutaneous leishmaniasis (CL), although responsible for controlling the infection, is associated with the pathogenesis of disease. Conversely, the immune response induced by S. mansoni antigens is able to prevent immune-mediated diseases. The aim of this study was to evaluate the potential of the S. mansoni Sm29 antigen to change the profile of monocyte-derived dendritic cells (MoDCs) from subjects with cutaneous leishmaniasis (CL) in vitro. Monocytes derived from the peripheral blood mononuclear cells of twelve patients were cultured with GM-CSF and IL-4 for differentiation into dendritic cells and then stimulated with soluble Leishmania antigen (SLA) in the presence or absence of Sm29 antigen. The expression of surface molecules associated with maturation and activation (HLA-DR, CD40, CD83, CD80, and CD86), inflammation (IL-12, TNF), and downregulation (IL-10, IL-10R) was evaluated using flow cytometry. We observed that the frequencies of HLA-DR, CD83, CD80, and CD86 as well as of IL-10 and IL-10R on MoDCs were higher in cultures stimulated with Sm29, compared to the unstimulated cell cultures. Our results indicate that the Sm29 antigen is able to activate regulatory MoDCs in patients with cutaneous leishmaniasis. It might be useful to control the inflammatory process associated with this disease.

Susceptibility of dendritic cells from individuals with schistosomiasis to infection by Leishmania braziliensis

“…Data from our group showed that dendritic cells from patients with cutaneous leishmaniasis increased IL-10R + expression after stimulation with Schistosoma mansoni tegument antigen (rSm29) and soluble Leishmania antigen (SLA) when compared to cultures stimulated with SLA alone (Lopes et al, 2014). …”

Schistosoma mansoni rSm29 Antigen Induces a Regulatory Phenotype on Dendritic Cells and Lymphocytes From Patients With Cutaneous Leishmaniasis

“…Regarding the expression of HLA-DR, a molecule associated with antigen presentation, we observed that stimulation by rSm29 or LPS did not change the mean fluorescence intensity of this molecule in the MoDCs infected or uninfected by L. braziliensis when compared to non-stimulated cultures. Previous data from our group showed that rSm29 stimulation in MoDC cultures from patients with CL yielded HLA-DR expression similar to non-stimulated cells (22). On the other hand, monocytes from CL patients stimulated with rSm29 had lower HLA-DR expression compared to non-stimulated cells (21).…”

“…Another study by Bafica et al reported that monocytes from patients with CL stimulated by the rSm29 and soluble Leishmania braziliensis antigen (SLA) antigen had lower HLA-DR expression compared to SLA-stimulated cells only (21). Previous studies performed by our group showed that MoDCs from patients with CL when stimulated with rSm29 and SLA expressed more maturation (CD83) and costimulatory molecules (CD80 and CD86) in relation to non-stimulated cells or cells stimulated with SLA only (22). These unconventional activations of MoDCs have provided the rationale for the use of recombinant Sm29 antigen in in vitro studies with cells from patients with leishmaniasis infected by L. brazileinsis in an attempt to modulate the inflammatory response associated with pathogenesis.…”

“…Our study also showed that the frequency of cells expressing the IL-10 receptor (IL-10R) is increased in the rSm29-stimulated co-cultures, both in the MoDCs infected and not infected by L. braziliensis . Previously, we had demonstrated that MoDCs of individuals with CL stimulated with rSm29 and SLA had increased IL-10R expression compared to non-stimulated cells, cells stimulated only with SLA, or cells stimulated with rSm29 alone (22). A study published by Faria et al showed that IL-10R expression deficiency in situ in the lesion would be associated with the exaggerated response observed in mucosal leishmaniasis when compared to CL (41).…”

A double edged sword: Schistosoma mansoni Sm29 regulates both Th1 and Th2 responses in inflammatory mucosal diseases

“…We observed that Sm29 led to an increase in the frequency of DCs expressing IL-10 and IL-10 receptor (IL-10R) in patients with CL. 18 IL-10 may act in the control of cell-mediated lesion development in leishmaniasis. In mucosal leishmaniasis (ML) there is a lack of IL-10 response, in part explained by the downregulation of the IL-10R.…”