The Regulatory Effect of Cortisol on the Immune Response in Canine Visceral Leishmaniasis

• Grant number: 23/04680-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2023
• End date: January 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Valéria Marçal Felix de Lima
• Grantee: Lucas Takeshi Siqueira Ito
• Host Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Canine Leishmaniasis (LCan) is a zoonosis caused by the protozoan of the genus Leishmania, with Leishmania infantum being the predominant etiological agent in Brazil. In endemic areas, there is an important correlation in the prevalence of the disease in humans and seropositive dogs. Therefore, the dog is an important target in disease control measures. In CanL, the cellular immune response (Th1) is inefficient to fight the parasite concomitantly with the increase in the humoral immune response (Th2).Some pro-inflammatory cytokines regulate and act on the Hypothalamus-Pituitary-Adrenal axis, causing increased production of corticotropin-releasing hormone by the hypothalamus and induces the pituitary gland to synthesize adrenocorticotropic hormone (ACTH) and the adrenal glands to produce steroids, glucocorticoids, dehydroepiandrosterone and ester sulfate that can modulate the immune response. Different experimental models of infection show that such an imbalance of the HPA axis prevents the host from mounting an adequate endocrine immune response, which in turn may influence disease susceptibility.Still as a bidirectional system, glucocorticoids modify the immune function, decreasing the production of pro-inflammatory cytokines and increasing the stimuli for the production of anti-inflammatory cytokines, leading to an imbalance of the Th1/Th2 type response, which is observed in the response Immune from CanL.The high level of cortisol and its regulatory role in the immunopathogenesis of the disease has already been studied in an experimental model , suggesting an important role for this hormone in the immune response of the disease. However, the relationship between hormonal disorders and immune regulation in CanL has not been evaluated. The discovery of these mechanisms may be important for a better understanding of the disease and its use in new therapeutic strategies.