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Etiopathogenesis of Leptospirosis: contribution of the complement system for the control of infection in vivo and in vitro and inflammatory response: identification of gene polymorphisms of the complement system in Leptospirosis patients

Abstract

Leptospirosis is one of the most important zoonosis worldwide, affecting especially underdeveloped countries with mild and tropical temperatures. Leptospirosis is considered a neglected disease and the immune mechanisms responsible for its control are not well known. The complement system is important for Leptospire killing and pathogenic species use a variety of strategies to evade this system, thereby allowing them to disseminate in the host for longer periods of time. A detailed understanding of how pathogenic Leptospires escape the complement system is an important challenge in biomedical sciences. In this thematic project, we plan to explore in more detail a number of questions regarding the mechanisms of immune evasion by Leptospires. Specifically, we plan to investigate: 1) the role of C3 in the control of Leptospirosis, both in vivo and in vitro, and in the etiopathogenesis responsible for the acute and chronic lesions in the liver and kidneys of infected animals; 2) what are the complement activation pathways involved in Leptospire killing; 3) how are thermolysins, metalloproteases secreted by pathogenic Leptospires, regulated and activated and what are the consequences of heterologous expression of these proteases by a non-pathogenic Leptospira species and, 4) correlations between the polymorphism of certain complement genes and disease severity in Leptospirosis patients. Detailed investigation of the complement activation pathways involved in Leptospira killing and mechanisms of phagocytosis evasion by pathogenic Leptospires will shed light on unresolved questions regarding Leptospira pathogenesis. In addition, the development of new genetic tools will allow us to genetically manipulate Leptospires in order to test hypothesis related to the functions of specific genes and the identification and characterization of specific Leptospira virulence factors. (AU)

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Scientific publications (10)
(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)
BARBOSA, ANGELA SILVA; ISAAC, LOURDES. Strategies used byLeptospiraspirochetes to evade the host complement system. FEBS Letters, v. 594, n. 16, SI, p. 2633-2644, . (18/12896-2, 17/12924-3)
BARBOSA, ANGELA SILVA; ISAAC, LOURDES. Strategies used by Leptospira spirochetes to evade the host complement system. FEBS Letters, v. 594, n. 16, p. 12-pg., . (18/12896-2, 17/12924-3)
SANTIESTEBAN-LORES, LAZARA ELENA; CARNEIRO, MILENA CARVALHO; ISAAC, LOURDES; BAVIA, LORENA. Complement System in Alcohol-Associated Liver Disease. Immunology Letters, v. 236, p. 37-50, . (17/12924-3, 19/19800-3, 07/03393-2)
BARBOSA, ANGELA SILVA; ISAAC, LOURDES. Strategies used byLeptospiraspirochetes to evade the host complement system. FEBS Letters, . (17/12924-3, 18/12896-2)
OKOCHI ALVES DA SILVA, PRISCILLA YURI; MIDON, LEONARDO MOURA; HEINEMANN, MARCOS BRYAN; VASCONCELOS, DEWTON DE MORAES; BARBOSA, ANGELA SILVA; ISAAC, LOURDES. Contribution of Complement System pathways to the killing of Leptospira spp.. Microbes and Infection, v. 22, n. 10, p. 550-557, . (17/12924-3, 17/18936-3)
MACEDO, ANA CATARINA LUNZ; LORES, LAZARA ELENA SANTISTEBAN; ALBUQUERQUE, JOSE ANTONIO TAVARES; DUARTE, NILO JOSE COELHO; ROMANO, PASCHOALINA; EBNER, PERSIO ALMEIDA REZENDE; REZENDE, VINICIUS MARCONDES; SILVA, CLOVIS A. A.; ANDRADE, LUIS EDUARDO COELHO; VASCONCELOS, DEWTON MORAES; et al. A rare association between factor H deficiency and lupus: Case report and experimental treatment with curcumin. FRONTIERS IN PEDIATRICS, v. 10, p. 8-pg., . (17/12924-3, 10/50043-0)
MARTINEZ, ADRIANA PATRICIA GRANADOS; ABREU, PATRICIA ANTONIA ESTIMA; DE ARRUDA VASCONCELLOS, SILVIO; HO, PAULO LEE; FERREIRA, VIVIANA P.; SAGGU, GURPANNA; BARBOSA, ANGELA SILVA; ISAAC, LOURDES. The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa. FRONTIERS IN IMMUNOLOGY, v. 11, . (17/12924-3)
SANTIESTEBAN-LORES, LAZARA ELENA; AMAMURA, THAIS AKEMI; DA SILVA, TIAGO FRANCISCO; MIDON, LEONARDO MOURA; CARNEIRO, MILENA CARVALHO; ISAAC, LOURDES; BAVIA, LORENA. A double edged-sword - The Complement System during SARS-CoV-2 infection. Life Sciences, v. 272, . (19/19800-3, 17/10208-9, 17/12924-3, 18/26574-7, 19/01435-7)
AZEVEDO, ISABELA RESENDE; AMAMURA, THAIS AKEMI; ISAAC, LOURDES. Human leptospirosis: In search for a better vaccine. Scandinavian Journal of Immunology, v. 98, n. 5, p. 21-pg., . (20/16104-3, 17/10208-9, 17/12924-3)
COURROL, DANIELLA DOS SANTOS; DA SILVA, CRISTIANE CASTILHO FERNANDES; PRADO, LUAN GAVIAO; CHURA-CHAMBI, ROSA MARIA; MORGANTI, LIGIA; DE SOUZA, GISELE OLIVEIRA; HEINEMANN, MARCOS BRYAN; ISAAC, LOURDES; CONTE, FERNANDO PAIVA; VIEIRA PORTARO, FERNANDA CALHETA; et al. Leptolysin, a Leptospira secreted metalloprotease of the pappalysin family with broad-spectrum activity. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 20-pg., . (18/12896-2, 19/22706-9, 17/12924-3)

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