Biochemical and functional studies of glycoconjugates (LPGs / GIPLs) and prospection of LRV virus in rare dermotropic species/strains of Leishmania.

• Grant number: 21/01243-0
• Support Opportunities: Research Grants - Visiting Researcher Grant - Brazil
• Start date: June 01, 2021
• End date: May 31, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcia Dalastra Laurenti
• Grantee: Marcia Dalastra Laurenti
• Visiting researcher: Rodrigo Pedro Pinto Soares
• Visiting researcher institution: Ministério da Saúde (Brasil). Fundação Oswaldo Cruz (Fiocruz). Centro de Pesquisas René Rachou (Fiocruz Minas), Brazil
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The dermotropic species of Leishmania cause a wide spectrum of clinical manifestations ranging from benign cutaneous lesions (ulcerated or not) to desfiguring and severe manifesations such as muco-cutaneous and disseminated. Brazil, especially in the Amazon, is considered the area with the highest biodiversity of Leishmania species. Some of them are rare and not well studied. In this project, we will study some of these species focusing on the purification of surface glycoconjugates (LPGs and GIPLs). We will evaluate them functionally in immunopathological assays. We aim to establish if interspecies polymorphisms in those molecules will affect the immunomodulation of inflammatory mediators (NO and cytokines). We intend to correlate if chemical variations with pro-inflammatory activity by dermotropic species and to develop an animal model in hamster. Recently, we reported that LPGs from dermotropic L. infantum strains, a common viscerotropic species, were more pro-inflammatory than those from viscerotropic strains (Cardoso et al., 2020). Those findings were very exciting once this pioneer study between our groups showed that the atypical strains of L. infantum were behavouring siimilar to dermotropic typical strains of L. braziliensis, L. shawi and L. amazonensis (Passero et al. 2015; Ibraim et al., 2013; Nogueira et al., 2016 e Vieira et al., 2019). Then, in this project, we intendo to expand the study of the glycobiology and imnunopathology of rare dermotropic species from the Amazon region. Those include: Leishmania lindembergui, Leishmania lainsoni, Leishmania naiffi and Leishmania guyanensis. As controls, we will include L. shawi and L. braziliensis already studied by our groups. Also, we intend to evaluate if the dermotropic Honduran strains of L. infantum are infected with the LRV virus alike L. braziliensis and L. guynanensis. This virus is related to a higher virulence in the strains from the subgenus Viannia. However, we do not know if its variant (LRV2) is present in dermotropic L. infantum. This project aims to undertand several gaps in the glycobiology and immunoparasitology of dermotropic strains of the subgenera Viannia and Leishmania. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVEIRA, MURILO BARROS; GOMES, RODRIGO SAAR; SHIO, MARINA TIEMI; RUGANI, JERONIMO NUNES; PARANAIBA, LARISSA FERREIRA; SOARES, RODRIGO PEDRO; RIBEIRO-DIAS, FATIMA. Lipophosphoglycan From Dermotropic New World Leishmania Upregulates Interleukin-32 and Proinflammatory Cytokines Through TLR4 and NOD2 Receptors. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 12-pg., 2022-03-23. (21/01243-0)

REGO, FELIPE D.; CARDOSO, CAMILA D. A.; MOREIRA, PAULO OTAVIO L.; NOGUEIRA, PAULA M.; ARAUJO, MARCIO S.; BORGES, VALERIA MATOS; LAURENTI, MARCIA D.; BARTHOLOMEU, DANIELLA C.; REIS, ALEXANDRE B.; MONTE-NETO, RUBENS L. D.; et al. Leishmania amazonensis from distinct clinical forms/hosts has polymorphisms in Lipophosphoglycans, displays variations in immunomodulatory properties and, susceptibility to antileishmanial drugs. Cell Biology International, v. 46, n. 11, p. 12-pg., 2022-08-23. (20/05388-0, 21/01243-0)