Characterization and therapeutic potential of chemokine action in sepsis and Flavivirus-induced encephalitis

• Grant number: 18/10990-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2019
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Agreement: Research Foundation - Flanders (FWO)
• Principal Investigator: Rafael Elias Marques Pereira Silva
• Grantee: Rafael Elias Marques Pereira Silva
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Inflammation assists in the defense against viral and bacterial infections, but needs to be tightly controlled. Indeed, an insufficient immunological response may fail to clear pathogens from the body, while overactivation or inappropriate downregulation of inflammation may lead to permanent tissue damage. Chemokines are crucial players in inflammatory reactions and are regulated by transcription and translation of chemokine ligands and receptors, posttranslational modification and interaction with glycosaminoglycans. Immunoassays quantify the total amount of a specific chemokine protein but seldom discriminate between post-translationally modified forms that often possess a different biological activity and receptor specificity. Moreover, despite current in vitro evidence that chemokine modifications and interactions with glycosaminoglycans are important, limited information is available on their role in vivo, e.g. in infection. We wish to integrate the complementary expertise of partners in Leuven and São Paulo to improve our understanding on the role of chemokines in viral and bacterial infection (using sepsis and viral encephalitis models), specifically with regard to the effect of chemokine post-translational modification and interaction with glycosaminoglycans on the outcome of infection and inflammation. This should improve our understanding of the immune response during the infection process and eventually lead to a better drug target selection. (AU)

Scientific publications

(7)

(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)

ROCHA, REBECA FROES; DEL SARTO, JULIANA L.; GOMES, GIOVANNI F.; GONCALVES, MARIANA P.; RACHID, MILENE A.; SMETANA, JULIANA H. C.; SOUZA, DANIELE G.; TEIXEIRA, MAURO MARTINS; MARQUES, RAFAEL ELIAS. Type I interferons are essential while type II interferon is dispensable for protection against St. Louis encephalitis virus infection in the mouse brain. VIRULENCE, v. 12, n. 1, p. 244-259, JAN 1 2021. (18/03917-6, 18/10990-1)

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)

DE CARVALHO, ANA CAROLINA; DIAS, CARLOS SATO B.; COIMBRA, LAIS D.; ROCHA, REBECA P. F.; BORIN, ALEXANDRE; FONTOURA, MARINA A.; CARVALHO, MURILO; PROOST, PAUL; NOGUEIRA, MAURICIO L.; CONSONNI, SILVIO R.; et al. Characterization of Systemic Disease Development and Paw Inflammation in a Susceptible Mouse Model of Mayaro Virus Infection and Validation Using X-ray Synchrotron Microtomography. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 5, p. 17-pg., 2023-03-01. (18/02594-9, 18/02993-0, 18/03917-6, 18/10990-1)

SILVA, BRUNA M.; GOMES, GIOVANNI F.; VERAS, FLAVIO P.; CAMBIER, SEPPE; SILVA, GABRIEL V. L.; QUADROS, ANDREZA U.; CAETITE, DIEGO B.; NASCIMENTO, DANIELE C.; SILVA, CAMILLA M.; SILVA, JULIANA C.; et al. C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps. Journal of Clinical Investigation, v. 133, n. 12, p. 18-pg., 2023-06-15. (13/08216-2, 20/04860-8, 18/10990-1)

FONTOURA, MARINA ALVES; ROCHA, REBECA FROES; MARQUES, RAFAEL ELIAS. Neutrophil Recruitment and Participation in Severe Diseases Caused by Flavivirus Infection. LIFE-BASEL, v. 11, n. 7, JUL 2021. (18/02594-9, 18/10990-1, 19/20772-4)

CAMBIER, SEPPE; METZEMAEKERS, MIEKE; DE CARVALHO, ANA CAROLINA; NOOYENS, AMBER; JACOBS, CATO; VANDERBEKE, LORE; MALENGIER-DEVLIES, BERT; GOUWY, MIEKE; HEYLEN, ELISABETH; MEERSSEMAN, PHILIPPE; et al. p Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza. JCI INSIGHT, v. 7, n. 1, JAN 11 2022. (18/10990-1)

METZEMAEKERS, MIEKE; CAMBIER, SEPPE; BLANTER, MARFA; VANDOOREN, JENNIFER; DE CARVALHO, ANA CAROLINA; MALENGIER-DEVLIES, BERT; VANDERBEKE, LORE; JACOBS, CATO; COENEN, SOFIE; MARTENS, ERIK; et al. Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019. CLINICAL & TRANSLATIONAL IMMUNOLOGY, v. 10, n. 4, 2021. (18/10990-1)