Immunological mechanisms of resistance and disease in malaria

• Grant number: 16/23618-8
• Support Opportunities: Research Projects - Thematic Grants
• Duration: June 01, 2018 - May 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: João Santana da Silva
• Grantee: João Santana da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Rodrigo Guerino Stabeli
• Associated researchers: Caroline Junqueira Giusta ; Dario Simões Zamboni ; Fernando de Queiroz Cunha ; Helder Takashi Imoto Nakaya ; João Santana da Silva ; José Carlos Farias Alves Filho ; Marcelo Urbano Ferreira ; Thiago Mattar Cunha
• Associated grant(s): 21/15127-2 - EMU granted in process 2016/23618-8: FACSymphony A5 SE Flow Cytometer, AP.EMU; 21/15132-6 - EMU granted in case 2016/23618-8: Cell Sorter Aria III CDU 5B/3R/6V, AP.EMU; 20/05527-0 - Bivalent intranasal vaccine using influenza virus expressing SARS-CoV-2 protein S (spike): protection mechanisms and lung injury, AP.R
• Associated scholarship(s): 22/03909-9 - Regulation of pathogenic gravity by interleukin IL-27 triggered in experimental infection by Plasmodium chabaudi, BP.IC; 21/12851-1 - Evaluation of the role of CD8+ T lymphocytes in recognition of proteins expressed in reticulocytes infected with Plasmodium vivax, BP.DD; 20/01043-9 - Immunological mechanisms of resistance and disease in Malaria, BP.PD

Abstract

In the last 15 years, my lab has dedicated to understand the mechanisms by which Plasmodium infection stimulate the innate immune responses and what is the outcome of these responses in host resistance to infection and pathogenesis of malaria. The current research program includes three projects around a main theme, which is "Immunological mechanisms of host resistance and disease in malaria". In the first project titled "Monocyte dendritic cells (MO-DCs) in malaria", we plan to evaluate the emergence of MO-DCs and the their pathogenic role in rodent malaria. In the second project titled "Killing of P. vivax infected reticulocytes by cytotoxic T cells" we provide evidences that P. vivax infected reticulocytes express HLA-I (MHC class I) and are killed by CD8+ T cells from malaria patients. We intent to evaluate the competence of reticulocytes to present endogenous antigens via HLA-I and the mechanism of intracellular parasite killing by CD8+ cytotoxic T cells. Finally, third project is titled "Immunology of asymptomatic malaria and the effects of immunity on Plasmodium transmission". In this project, we propose to identify innate immune biomarkers as well as B and T cell responses that are predictive of disease outcome and mosquito transmission. If successful, our studies will provide important information for monitoring silent infection in infective asymptomatic individuals and potentially new insights to further control malaria transmission in hypo-endemic areas. In summary, by using ex vivo, in vitro and in vivo experimental models, we intent to elaborate cell biology and immunological questions that will allow us to address the mechanisms of host resistance and pathogenesis of malaria. In the third project we intent to apply some of the hypothesis raised in the lab to define mechanisms that are potentially involved in modulating the systemic inflammation and preventing parasite elimination in asymptomatic malaria patients, and therefore, main impediment for eliminating parasite transmission in hypo-endemic areas of malaria. (AU)

Scientific publications

(8)

(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)

HIRAKO, ISABELLA C.; ASSIS, PATRICIA A.; GALVAO-FILHO, BRUNO; LUSTER, ANDREW D.; ANTONELLIL, LIS R. V.; GAZZINELLI, RICARDO T.. Monocyte-derived dendritic cells in malaria. Current Opinion in Microbiology, v. 52, p. 139-150, DEC 2019. (16/23618-8)

JUNQUEIRA, CAROLINE; BARBOSA, CAMILA R. R.; COSTA, PEDRO A. C.; TEIXEIRA-CARVALHO, ANDREA; CASTRO, GUILHERME; SEN SANTARA, SUMIT; BARBOSA, RAFAEL P.; DOTIWALA, FAROKH; PEREIRA, DHELIO B.; ANTONELLI, LIS R.; et al. Cytotoxic CD8(+) T cells recognize and kill Plasmodium vivax-infected reticulocytes. Nature Medicine, v. 24, n. 9, p. 1330+, SEP 2018. (16/23618-8)

PRIOR, KIMBERLEY F.; RIJO-FERREIRA, FILIPA; ASSIS, PATRICIA A.; HIRAKO, ISABELLA C.; WEAVER, DAVID R.; GAZZINELLI, RICARDO T.; REECE, SARAH E.. Periodic Parasites and Daily Host Rhythms. CELL HOST & MICROBE, v. 27, n. 2, p. 176-187, FEB 12 2020. (16/23618-8)

ALMEIDA, GREGORIO GUILHERME; CARVALHO COSTA, PEDRO AUGUSTO; ARAUJO, MAISA DA SILVA; GOMES, GABRIELA RIBEIRO; CARVALHO, ALEX FIORINI; FIGUEIREDO, MARIA MARTA; PEREIRA, DHELIO BATISTA; TADA, MAURO SHUGIRO; MEDEIROS, JANSEN FERNANDES; SOARES, IRENE DA SILVA; et al. symptomatic Plasmodium vivax malaria in the Brazilian Amazon: Submicroscopic parasitemic blood infects Nyssorhynchus darling. PLoS Neglected Tropical Diseases, v. 15, n. 10, OCT 2021. (16/23618-8)

PEREIRA, LARISSA M. N.; ASSIS, PATRICIA A.; DE ARAUJO, NATALIA M.; DURSO, DANIELLE F.; JUNQUEIRA, CAROLINE; ATAIDE, MARCO ANTONIO; PEREIRA, DHELIO B.; LIEN, EGIL; FITZGERALD, KATHERINE A.; ZAMBONI, DARIO S.; et al. Caspase-8 mediates inflammation and disease in rodent malaria. NATURE COMMUNICATIONS, v. 11, n. 1, SEP 14 2020. (16/23618-8)

ANTONELLI, LIS R.; JUNQUEIRA, CAROLINE; VINETZ, JOSEPH M.; GOLENBOCK, DOUGLAS T.; FERREIRA, MARCELO U.; GAZZINELLI, RICARDO T.. The immunology of Plasmodium vivax malaria. IMMUNOLOGICAL REVIEWS, v. 293, n. 1, SI, p. 163-189, JAN 2020. (16/23618-8)

JUNQUEIRA, CAROLINE; POLIDORO, RAFAEL B.; CASTRO, GUILHERME; ABSALON, SABRINA; LIANG, ZHITAO; SEN SANTARA, SUMIT; CRESPO, ANGELA; PEREIRA, DHELIO B.; GAZZINELLI, RICARDO T.; DVORIN, JEFFREY D.; et al. gamma delta T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis. NATURE IMMUNOLOGY, v. 22, n. 3, JAN 2021. (16/23618-8)

DINIZ, SUELEN QUEIROZ; TEIXEIRA-CARVALHO, ANDREA; FIGUEIREDO, MARIA MARTA; CARVALHO COSTA, PEDRO AUGUSTO; ROCHA, BRUNO COELHO; MARTINS-FILHO, OLINDO ASSIS; GONCALVES, A. RICARDO; PEREIRA, DHELIO BATISTA; TADA, MAURO SHUGIRO; OLIVEIRA, FABIANO; et al. Plasmodium vivax Infection Alters Mitochondrial Metabolism in Human Monocytes. MBIO, v. 12, n. 4, JUL-AUG 2021. (16/23618-8)