Understanding the role of neutrophil recruitment and activation in arboviral diseases

• Grant number: 21/05519-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2022
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Research Foundation - Flanders (FWO)
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Rafael Elias Marques Pereira Silva
• Principal researcher abroad: Paul Proost
• Institution abroad: University of Leuven, Leuven (KU Leuven), Belgium
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated researchers: Fernando de Queiroz Cunha ; Jennifer Vandooren ; José Carlos Farias Alves Filho ; Pedro Elias Marques Pereira Silva ; Sofie Struyf

Abstract

As first cells recruited to inflammatory sites, neutrophils weaken infections, but also cause excessive tissue destruction and immunopathology. Neutrophils are known to be crucial to clear bacterial pathogens, but their contribution to host defense and response to viral diseases, e.g. arbovirus-induced encephalitis or arthritogenic disease are much less understood. Indeed, seen as secondary players in viral infection control, the role of neutrophils in development, severity and resolution of viral encephalitis has been neglected. Molecules involved in neutrophil recruitment and invasion of the central nervous system remain unclear, as are the effector mechanisms unleashed by neutrophils when encountering infected and damaged cells. We will investigate in detail effects of arboviral infections on neutrophil recruitment and activation and correlate neutrophil activity in tissue to disease severity. Our approach will combine models of infection with St. Louis encephalitis virus and Mayaro virus and advanced techniques such as intravital microscopy to evaluate the inflammatory milieu in tissues. We will identify the chemokines and adhesion molecules driving neutrophil infiltration, activation and viral clearance. Neutrophil effector mechanisms will be investigated with pharmacological inhibitors or using knock-out mice. This project will uncover the role of neutrophils in neglected arboviral diseases and propose new strategies to control disease severity and inflammatory damage. (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)

NACIUK, FABRICIO FREDO; NASCIMENTO, ANDREY FABRICIO ZIEM; ROCHA, REBECA PAIVA FROES; RUSTIGUEL, JOANE KATHELEN; COIMBRA, LAIS DURCO; MARQUES, RAFAEL ELIAS; BRUDER, MARJORIE. Competing interests during the key N-glycosylation of 6-chloro-7-deaza-7-iodopurine for the synthesis of 7-deaza-2'-methyladenosine using Vorbruggen conditions. RONTIERS IN CHEMISTR, v. 11, p. 9-pg., 2023-03-23. (21/05519-0, 18/10990-1)

SOTORILLI, GIULIANA EBOLI; GRAVINA, HUMBERTO DORIGUETTO; DE CARVALHO, ANA CAROLINA; SHIMIZU, JACQUELINE FARINHA; FONTOURA, MARINA ALVES; MELO-HANCHUK, TALITA DINIZ; CORDEIRO, ARTUR TORRES; MARQUES, RAFAEL ELIAS. Phenotypical Screening of an MMV Open Box Library and Identification of Compounds with Antiviral Activity against St. Louis Encephalitis Virus. Viruses-Basel, v. 15, n. 12, p. 16-pg., 2023-12-01. (18/10990-1, 21/05519-0, 18/02993-0)

MARQUES, RAFAEL ELIAS; SHIMIZU, JACQUELINE FARINHA; NOGUEIRA, MAURICIO LACERDA; VASILAKIS, NIKOS. Current challenges in the discovery of treatments against Mayaro fever. EXPERT OPINION ON THERAPEUTIC TARGETS, v. 28, n. 5, p. 12-pg., 2024-05-10. (22/03645-1, 21/05519-0)