P015 TSLP enhances type 1 immune response in cutaneous leishmaniasis patients

Abstract

Introduction Leucocytes from cutaneous leishmaniasis (CL) patients due to L. braziliensis infection secrete high levels of IFN-gamma and TNF-alpha in response to soluble Leishmania antigen (SLA) and at lesion site. This type of immune response helps to control parasite multiplication but also mediates tissue damage and lesion development. Thus, we think CL patients would benefit from a balanced Th1/Th2 immune response. It has been shown that cells that do not classically participate in immune response, such as epithelial cells, can secrete soluble factors interfering on T cells responses to pathogens. Thymic stromal lymphopoietin (TSLP) is a recently described cytokine secreted by epithelial cells. TSLP-activated macrophages and dendritic cells enhance IL-4 and IL-13 secretion by memory CD4+ T cells in asthma and helminthes infections. Methods Peripheral blood mononuclear cells were obtained from CL individuals. Cells were stimulated with soluble Leishmania antigen or D. pteronyssinus in presence or absence of recombinant TSLP for 72 h. Cytokines were measured in cell culture supernatants by ELISA. For immunohistochemistry, biopsies were obtained from CL patients and stained for TSLP. Results Since TSLP induces Th2 responses, our hypothesis was that presence of TSLP would conditionate antigen presenting cells to enhance SLA-induced Th2 responses in CL patients decreasing levels of Th1 cytokines. Surprisingly, our data shows that in presence of TSLP, SLA-stimulated PBMC from CL individuals enhance IFN-gamma production, instead. No change in SLA-induced IL-5, TNF-alpha and IL-10 was observed. To test the effect of TSLP on antigens known to induce Th2 responses, we stimulated cells from the same patients with D. pteronyssinus (Derp) antigen in presence or absence of TSLP. As expected, presence of TSLP enhanced Derp-induced IL-5 production. The fact that TSLP can be expressed by skin epithelial cells, led us to investigate whether there was presence of TSLP in lesion of CL patients. Immunohistochemistry reveled TSLP expression in epithelial cells, endothelial cells and macrophages from CL individuals. We finally asked if Leishmania infection would interfere on TSLP receptor expression in monocytes. L. braziliensis-infected monocytes from healthy individuals up-regulated TSLP receptor expression. Conclusion Our results show a novel role for TSLP in inducing up-regulation of IFN-gamma production in CL patients. These data suggest that presence of TSLP may contribute for parasite killing and also maintenance of inflammatory response in these patients.