LncRNAs and mRNA in splenic macrophages of dogs with visceral leishmaniasis and immune regulation by Malat-1

• Grant number: 25/08317-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Valéria Marçal Felix de Lima
• Grantee: Valéria Marçal Felix de Lima
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Alexandre Rossi Paschoal ; Flavia Lombardi Lopes

Abstract

Domestic dogs are the main urban reservoirs of Leishmania infantum, the causative agent of Visceral Leishmaniasis (VL) in the Americas. In VL-endemic regions, the number of human cases is associated with the rate of canine infection. In CanL, sick dogs mount an inefficient cellular immune response (Th1) to combat the parasite concomitantly with an increased humoral immune response (Th2). In sick dogs, non-coding microRNAs induced in disease target sites such as the spleen and peripheral blood by the infectious process can modulate immunity by interfering with the Th1 and Th2 balance. Recently, another class of long non-coding RNAs, LncsRNAs, have been recognized as gene regulators in the immune system. LncsRNAs can regulate gene expression by multiple mechanisms; the interaction of LncRNAs with RNA, proteins and DNA influences the chromatin structure and function of nearby and distant genes, promoting the regulation of gene expression. LncsRNAs can regulate the development and homeostasis of the innate and adaptive immune response and play a key role in autoimmune diseases and inflammatory pathways. In tumor processes, their immunoregulatory function is well characterized, but their role in the regulation of immunity in infectious diseases is poorly understood. Recently, differential expression of MALAT-1 was reported in mononuclear cells from patients with visceral leishmaniasis and in experimental models, but its functional role in the regulation of immunity has not been characterized in canine visceral leishmaniasis. In mice infected with L. donovani, MALAT-1 appears to be associated with the production of IL-10 and increased PD-L1, suppressor molecules produced in dogs with leishmaniasis. Therefore, we will evaluate the differential expression of LncRNAs in splenic macrophages from dogs with leishmaniasis and the regulatory role of MALAT-1 in splenic leukocytes from dogs with leishmaniasis and its regulatory function in the target molecules already described. Knowledge of the factors associated with disease progression may provide relevant information for the development of new treatment strategies for canine leishmaniasis. (AU)