miR-148a regulation interferes in inflammatory cytokine and parasitic load in canine leishmaniasis.

Autor: Rebech GT; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Bragato JP; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Costa SF; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., de Freitas JH; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Dos Santos MO; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Soares MF; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Eugênio FR; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., Dos Santos PSP; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil., de Lima VMF; Department of Clinical Medicine, Surgery and Animal Reproduction, São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba, Brazil.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Jan 31; Vol. 17 (1), pp. e0011039. Date of Electronic Publication: 2023 Jan 31 (Print Publication: 2023).
DOI: 10.1371/journal.pntd.0011039
Abstrakt: Canine leishmaniasis (CanL) is a severe public health threat. Infected animals mediate transmission of the Leishmania protozoan to humans via the sandfly's bite during a blood meal. CanL progression depends on the degree of suppression of the immune response, possibly associated with microRNAs (miR), which can modulate mRNA translation into proteins and (consequently) regulate cell function. Increased miR-148a in splenic leukocytes (SL) of dogs with CanL was observed in previous studies, and in silico analysis, identified possible pathways involved in immune response regulation that are affected by this miR. Therefore, we evaluated the involvement of miR-148a in the regulation of TNF-α, IL-6, IL-12, IL-1β, iNOS, MHCII, CD80, CD3, T-bet, and GATA-3 transcription factors and their relationship with parasite load in SL of dogs with CanL. Splenic leukocytes obtained from healthy and diseased dogs were transfected with miR-148a mimic and inhibitor oligonucleotides. After 48 hours, expression levels of MHCII, CD80, iNOS, CD3, T-bet, and GATA-3 were evaluated by flow cytometry, and concentrations of TNF-α, IL-12, IL-6, and IL-1β were measured in culture supernatants by capture enzyme-linked immunosorbent assays. Transfection of SL with miR-148a mimics decreased iNOS levels in cells and TNF-α, IL-6, and IL-12 in the supernatants of cultured SL from CanL dogs. Interestingly, transfection with miR-148a inhibitor decreased parasite load in SL cells. These results suggest a direct or not regulatory role of this miR in the immune response to Leishmania infantum infection. We conclude that miR-148a can modulate immune responses by regulating inflammatory cytokines during CanL. Our results contribute to understanding the complex host/parasite interaction in CanL and could assist the development of treatments.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Rebech et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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