Combined in vitro IL-12 and IL-15 stimulation promotes cellular immune response in dogs with visceral leishmaniasis

Author(s):Show less -

Costa, Sidnei Ferro ^[1] ; Gomes, Vinicius Oliveira ^[1] ; dos Santos Maciel, Marilene Oliveira ^[1] ; Melo, Larissa Martins ^[1] ; Venturin, Gabriela Lovizutto ^[1] ; Bragato, Jaqueline Poleto ^[1] ; Rebech, Gabriela Torres ^[1] ; Santos, Catiule de Oliveira ^[2] ; Nascimento de Oliveira, Barbara Maria ^[2] ; de Sa Oliveira, Geraldo Gileno ^[2] ; Felix de Lima, Valeria Marcal ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Vet Med, Dept Anim Clin Surg & Anim Reprod, Aracatuba - Brazil

^[2] Fundacao Oswaldo Cruz, Goncalo Moniz Res Ctr, Lab Struct & Mol Pathol LAPEM, Rua Waldemar Falcao, Salvador, BA - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 14, n. 1 JAN 2020.
• Web of Science Citations: 0

Abstract

Domestic dogs are the main reservoir of Leishmania infantum, a causative agent of visceral leishmaniasis (VL). The number of human disease cases is associated with the rate of canine infection. Currently available drugs are not efficient at treating canine leishmaniasis (CanL) and months after the treatment most dogs show disease relapse, therefore the development of new drugs or new therapeutic strategies should be sought. In CanL, dogs lack the ability to mount a specific cellular immune response suitable for combating the parasite and manipulation of cytokine signaling pathway has the potential to form part of effective immunotherapeutic methods. In this study, recombinant canine cytokines (rcalL-12, rcalL-2, rcalL-15 and rcalL-7) and soluble receptor IL-10R1 (rcasIL-10R1), with antagonistic activity, were evaluated for the first time in combination (rcalL-12/rcalL-2, rcalL-12/rcalL-15, rcalL-12/rcasIL-10R1, rcalL-15/rcalL-7) or alone (rcasIL-10R1) to evaluate their immunomodulatory capacity in peripheral blood mononuclear cells (PBMCs) from dogs with leishmaniasis. All the combinations of recombinant proteins tested were shown to improve lymphoproliferative response. Further, the combinations rcalL-12/rcalL-2 and rcalL-12/rcalL-15 promoted a decrease in programmed cell death protein 1 (PD-1) expression in lymphocytes. These same combinations of cytokines and rcalL-12/rcasIL-10R1 induced IFN-gamma and TNF-alpha production in PBMCs. Furthermore, the combination IL-1211L-15 led to an increased in T-bet expression in lymphocytes. These findings are encouraging and indicate the use of rcalL-12 and rcalL-15 in future in vivo studies aimed at achieving polarization of cellular immune responses in dogs with leishmaniasis, which may contribute to the 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