Evaluating the role of interleukin-11 in the pathogenesis of cutaneous leishmaniasis and its implications in bacterial co-infections.

• Grant number: 24/05233-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Camila de Almeida Lopes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

Leishmaniasis is a neglected tropical disease that predominantly affects populations in tropical and subtropical regions of Africa, Asia, and Latin America, with approximately 12 million global cases and 1.5-2 million new cases annually. The infection can be caused by 20 species of pathogens, resulting in visceral or cutaneous forms of the disease, ranging from localized lesions to mucocutaneous involvement. The immune response against Leishmania is initiated when parasite molecules are detected by innate sensors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), present in cells like macrophages, neutrophils, monocytes, and keratinocytes. Additionally, activation of inflammasomes, protein complexes responsible for triggering pro-inflammatory pathways of the innate immune system, plays a central role in the immune response during Leishmania infection. Studies have shown that various mediators, including pro-inflammatory cytokines, including Interleukin-11 (IL-11), are related to the pathogenesis of Leishmaniasis, potentially leading to inflammasome activation. IL-11, a member of the IL-6 family, activates signaling pathways such as JAK-STAT and ERK, inducing epithelial, stromal, and endothelial cells to cause inflammation, fibrosis, and disruption of endogenous tissue repair, playing a key role in inflammatory and autoimmune diseases. Previous studies have reported increased expression of IL-11 in lesions of patients with cutaneous leishmaniasis, and IL-11 has been associated with the expression of genes related to NLRP3 inflammasome activation in monocytes. Moreover, other studies have shown that IL-11 contributes to the control of bacterial infections by regulating the inflammatory response and epithelial barrier integrity. Therefore, understanding the role of interleukin-11 during Leishmania infection and in bacterial co-infections is crucial for elucidating the immunological mechanisms involved in the pathogenesis of Leishmaniasis, as well as identifying key factors in host immune response regulation.