IL-10 receptor blockade controls the in vitro infectivity of Leishmania infantum and promotes a Th1 activation in PBMC of dogs with visceral leishmaniasis.
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Date
2021
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Abstract
An important strategy to reduce the risk of visceral leishmaniasis (VL) in humans is to control the infection and
disease progression in dogs, the domestic reservoir of Leishmania infantum parasites. Certain therapeutic strategies that modulate the host immune response show great potential for the treatment of experimental VL,
restoring the impaired effector functions or decreasing host excessive responses. It is known that the overproduction of interleukin-10 (IL-10) promotes parasite replication and disease progression in human VL as well
as in canine visceral leishmaniasis (CVL). Thus, in the present study we investigated the potential of the anticanine IL-10 receptor-blocking monoclonal antibody (Bloq IL-10R) to control and reduce in vitro infectivity of
L. infantum and improve the ability of PBMC isolated from VL dogs to alter the lymphoproliferative response and
intracytoplasmic cytokines. Overall, GFP+ Leishmania showed lower capacity of in vitro infectivity in the presence
of Bloq IL-10R. Moreover, addition of Bloq IL-10R in cultured PBMC enhanced T-CD4 and CD8 proliferative
response and altered the intracytoplasmic cytokine synthesis, reducing CD4+IL-4+ cells and increasing CD8+IFNγ+ cells after specific antigen stimulation in PBMC of dogs. Furthermore, we observed an increase of TNF-α levels
in supernatant of cultured PBMC under IL-10R neutralizing conditions. Together, our findings are encouraging
and reaffirm an important factor that could influence the effectiveness of immune modulation in dogs with VL
and suggest that blocking IL-10R activity has the potential to be a useful approach to CVL treatment.
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Keywords
Canine visceral leishmaniasis, Anti-canine IL-10 receptor-blocking monoclonal antibody, Immunotherapy
Citation
CARDOSO, J. M. de O. et al. IL-10 receptor blockade controls the in vitro infectivity of Leishmania infantum and promotes a Th1 activation in PBMC of dogs with visceral leishmaniasis. Molecular Immunology, v. 137, p. 20-27, 2021. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0161589021001899?via%3Dihub>. Acesso em: 11 out. 2022.