miR-150 regulates the Leishmania infantum parasitic load and GZMB levels in peripheral blood mononuclear cells of dogs with canine visceral leishmaniasis.

Author(s)

Matheus Fujimura Soares

• Document type: Master's Dissertation
• Press: Araçatuba. 2022-11-30.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária. Araçatuba
• Defense date: 2022-10-27
• Advisor: Valéria Marçal Felix de Lima

Abstract

Leishmania infantum causes visceral leishmaniasis, a neglected tropical disease that can modulate the host immune response by altering the expression of small non-coding RNAs called microRNAs (miRNAs). Some miRNAs are differentially expressed in peripheral blood mononuclear cells (PBMCs) of dogs with visceral canine leishmaniasis (CanL), like the down-regulated miR-150. Even though miR-150 is negatively correlated with L. infantum parasitic load, it is unclear if miR-150 directly affects L. infantum parasitic load and (if so) how this miRNA would contribute to infection. Here, we isolated PBMCs from 14 naturally infected dogs (CanL group) and six healthy dogs (Control group) and treated them in vitro with miR-150 mimic or inhibitor. We measured L. infantum parasitic load using qPCR and compared treatments. We also measured miR-150 in silico predicted target protein levels (STAT1, TNF-α, HDAC8, and GZMB) using flow cytometry or enzyme-linked immunosorbent assays. Increasing miR-150 activity diminished L. infantum parasitic load in CanL PBMCs. We also found that inhibition of miR-150 reduced GZMB levels. These findings demonstrate that miR-150 plays an important role in L. infantum infection in canine PBMCs, and these findings merit further studies aiming at drug development. (AU)

• FAPESP's process: 20/00565-1 - The role of miR-150 in the immune response against Leishmania infantum in dogs
• Grantee: Matheus Fujimura Soares
• Support Opportunities: Scholarships in Brazil - Master