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,Valeria Marçal Felix De Lima,Sidnei Ferro Costa,Diogo Rodrigo De Magalhães Moreira,Fabiana Santana Souza,Jessica Mariane Ferreira Mendes,Cristiane Garboggini Melo De Pinheiro,Geraldo Gileno De Sá Oliveira,Luciano Kalabric Silva,Yara M Traub-Csekö

doi:10.1371/journal.pone.0239171

Catiule De Oliveira Santos, Valeria Marçal Felix De Lima + Show 8 more

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https://doi.org/10.1371/journal.pone.0239171

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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.

Highlights

Cytokines are polypeptides that participate in communication between cells and the orchestration of immune system responses
CasIL-10R1 was defined as an array of 215 amino acids which exhibited 74% similarity to homologous region of human protein
Molecular weight and isoelectric point predicted for mature rcasIL-10R1 were 25.7 kDa and PI 8.3, respectively

Summary

Introduction

Cytokines are polypeptides that participate in communication between cells and the orchestration of immune system responses. In response to tissue damage and/or stimulation, these molecules may be secreted and bind to the extracellular domains of cognate receptors on target cells. This results in the phosphorylation of intracytoplasmic domains of cytokine receptors and activation of transcription factors, which migrate to the nucleus and implement cellular. Homologous soluble IL-10 receptor restores specific lymphoproliferative response in dogs with leishmaniasis

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