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| Author(s): |
Sidnei Ferro Costa
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Araçatuba. 2019-06-06. |
| Institution: | Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária. Araçatuba |
| Defense date: | 2019-05-20 |
| Advisor: | Valéria Marçal Felix de Lima |
| Abstract | |
Visceral Leishmaniasis (LV) is caused in the Americas by the obligate intracellular protozoan Leishmania infantum and domestic dogs are the major urban reservoirs of the parasite and in endemic areas, and increase LV in humans has been associated with increased canine infection. The current medications available for Canine Leishmaniasis (CanL) are not completely effective and months after treatment most dogs present with relapse, indicating the necessity to looking for alternative forms of treatment. In CanL, dogs develop an ineffective cellular immune response (Th1) to combat the parasite. Then, the stimulation of cytokine pathways in defense cells with recombinant proteins, has the potential to become part of effective immunotherapeutic methods. In this study, the canine recombinant cytokines (IL-12, IL-2, IL-15 and IL-7) and the soluble receptor of IL-10R1 (sIL-10R1) with antagonistic activity, were evaluated for the first time in combinations IL-12/IL-2, IL-12/IL-15, IL12/sIL-10R1, IL-15/IL-7) or alone (sIL-10R1) for their immunomodulatory capacity in peripheral blood mononuclear cells (PBMC) from dogs with leishmaniasis. All combinations of recombinant proteins tested were shown to improve lymphoproliferative response. Further, combinations of IL-12/IL-2 and IL-12/IL-15 promoted decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and IL-12/casIL-10R1 induced IFN-y production in PBMC. Furthermore, the combination of IL-12/IL-15 led to an increased T-bet expression . These findings encourage the use of IL-12 and IL-15 in future in vivo studies aiming to get polarization of cellular immune response in dogs with leishmaniasis, that may contribute to development of an effective treatment against CanL. (AU) | |
| FAPESP's process: | 17/10906-8 - Regulation of the T1 or T2 immune response with the use of recombinant cytokines in mononuclear cells of dogs with Visceral Leishmaniasis |
| Grantee: | Sidnei Ferro Costa |
| Support Opportunities: | Scholarships in Brazil - Master |