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

Sa Oliveira, G. G.; Santos, C. O.; Costa, S. F.; Souza, F. S.; Mendes, J. M. F.; Pinheiro, C. G. M.; Moreira, D. R. M.; Silva, L. K.; Lima, V. M. F.

doi:10.1101/2020.09.02.280610

bioRxiv · 10.1101/2020.09.02.280610

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

Sa Oliveira, G. G.·Santos, C. O.·Costa, S. F.·Souza, F. S.·Mendes, J. M. F.·Pinheiro, C. G. M.·Moreira, D. R. M.·Silva, L. K.·Lima, V. M. F.

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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 leishmaniasis caused by L. infantum (CanL) 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.

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Sa Oliveira, G. G., Santos, C. O., Costa, S. F., Souza, F. S., Mendes, J. M. F., Pinheiro, C. G. M., Moreira, D. R. M., Silva, L. K., Lima, V. M. F.. 2020-09-03. Blocking IL-10 signaling with soluble IL-10 receptor restores specific lymphoproliferative response in dogs with leishmaniasis caused by Leishmania infantum. https://doi.org/10.1101/2020.09.02.280610

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