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

Diego Mota Lopes,Lucas P Carvalho,Luciana Santos Cardoso,Sérgio Costa Oliveira,Edgar M Carvalho,Brady Page

doi:10.3389/fimmu.2018.03122

Abstract

The immune response induced by Schistosma mansoni antigens is able to prevent immune-mediated diseases. Conversely, the inflammatory response in cutaneous leishmaniasis (CL), although responsible for controlling the infection, is also associated with the pathogenesis of disease. The aim of this study was to evaluate the potential of the S. mansoni Sm29 antigen to change certain aspects of the profiles of monocyte derived dendritic cells (MoDCs) and lymphocytes from subjects with CL in vitro. Expression of surface molecules and intracellular cytokines in the MoDCs and lymphocytes as well as the proliferation of Leishmania braziliensis were evaluated by flow cytometry. Levels of cytokines were evaluated in culture supernatants by ELISA. It was observed that stimulation by rSm29 increased the frequency of expression of CD83, CD80, CD86, and IL-10R in MoDCs compared to non-stimulated cultures. Additionally rSm29 decreased the frequency CD4+ and CD8+ T cells expressing CD28 and increased the frequency of CD4+CD25hi and CD4+CTLA-4+ T lymphocytes. Addition of rSm29 to cultures increased IL-10 levels and decreased levels of IL-12p40 and IFN-γ, while not altering TNF levels compared to non-stimulated cultures. This study showed that rSm29 induced a regulatory profile in MoDCs and lymphocytes and thereby regulated the exaggerated inflammation observed in CL. Considering that there are few therapeutic options for leishmaniasis, the use of rSm29 may be an alternative to current treatment and may be an important strategy to reduce the healing time of lesions in patients with CL.

Highlights

Cutaneous leishmaniasis (CL) is an endemic disease in South and Central America, the Middle East, and Central Asia caused by a variety of Leishmania species
We evaluated the effect of the addition of the rSm29 antigen on monocyte-derived dendritic cells infected with L. braziliensis and co-cultured with autologous lymphocytes (MoDC-Ly) from patients with cutaneous leishmaniasis (CL)
We observed that the addition of the rSm29 antigen did not alter the MFI of HLA-DR in cultures of monocyte derived dendritic cells (MoDCs) infected with L. braziliensis [MFI: 87 [27–239]] or in uninfected cultures [MFI: 70 [10–246]] compared to non-stimulated cultures [infected MoDCs: 63 [28–268]; uninfected MoDCs: 72 [10–189], respectively] or cultures stimulated with LPS [infected MoDCs: 68 [27–252]; uninfected MoDCs: 59 [10–207], respectively, Figure 1B]

Summary

Introduction

Cutaneous leishmaniasis (CL) is an endemic disease in South and Central America, the Middle East, and Central Asia caused by a variety of Leishmania species. The various clinical manifestations of the disease are related to intrinsic rSm29 Antigen Modulates Cutaneous Leishmaniasis factors of the parasite and to factors related to the host immune response [2]. It is known that the Th1 immune response profile, if exaggerated, is the main cause of CL [3, 4]. Effector immunological mechanisms in CL lead to cellular and tissue destruction, culminating with the appearance of the characteristic ulcer that is the main clinical manifestation of CL. It is important to have a balance between Th1 and regulatory T cells, since both of these mechanisms are important in maintaining the tissue integrity of the host against an exaggerated inflammatory response [5, 6]

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Conclusion