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Blocking IL-10 signaling with soluble IL-10 receptor restores in vitro specific lymphoproliferative response in dogs with leishmaniasis caused by Leishmania infantum

Catiule De Oliveira Santos, Sidnei Ferro Costa, Fabiana Santana Souza, Jessica Mariane Ferreira Mendes, Cristiane Garboggini Melo de Pinheiro, , Luciano Kalabric Silva, Valeria Marçal Felix de Lima,
Published: 19 January 2021
PLOS ONE , Volume 16; doi:10.1371/journal.pone.0239171

Abstract: RIL-10 plays a major role in restricting exaggerated inflammatory and immune responses, thus preventing tissue damage. However, the restriction of inflammatory and immune responses by IL-10 can also favor the development and/or persistence of chronic infections or neoplasms. Dogs that succumb to canine leishmaniasis (CanL) caused by L. infantum develop exhaustion of T lymphocytes and are unable to mount appropriate cellular immune responses to control the infection. These animals fail to mount specific lymphoproliferative responses and produce interferon gamma and TNF-alpha that would activate macrophages and promote destruction of intracellular parasites. Blocking IL-10 signaling may contribute to the treatment of CanL. In order to obtain a tool for this blockage, the present work endeavored to identify the canine casIL-10R1 amino acid sequence, generate a recombinant baculovirus chromosome encoding this molecule, which was expressed in insect cells and subsequently purified to obtain rcasIL-10R1. In addition, rcasIL-10R1 was able to bind to homologous IL-10 and block IL-10 signaling pathway, as well as to promote lymphoproliferation in dogs with leishmaniasis caused by L. infantum.
Keywords: cytokines / Immune response / Lymphocytes / dogs / Leishmania / leishmaniasis / Recombinant proteins / Leishmania infantum

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