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Role of liver IL-1alpha in protection against superinfection during experimental malaria

Grant number: 15/25874-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 01, 2016
Effective date (End): April 30, 2017
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Maria Nogueira de Menezes
Supervisor: Maria Manuel Dias da Mota
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Universidade de Lisboa, Portugal  
Associated to the scholarship:13/09176-4 - Role of molecules that signalize cellular damage in experimental malaria, BP.DR


The understanding of host immune mechanisms during Plasmodium infection is essential to improve malaria prevention. In malaria endemic regions, one single person can be infected simultaneously with different species or strains of the same specie of Plasmodium, a phenomenon named superinfection. Semi-immune young children can be protected against superinfection. It was described in experimental rodent malaria that ongoing blood-stage infection can inhibit the development of secondary liver-stage infection. This protection is dependent on parasitemia and on the iron regulator hormone, hepcidin. Hepcidin levels increase in the liver during blood-stage Plasmodium chabaudi or Plasmodium berghei malaria. This augment leads to decrease of iron availability in hepatocytes, inhibiting the development of liver-stage forms of P. berghei. In addition, blood-stage infection causes intense liver inflammation and necrosis what, in turns, could protect against a subsequent infection with sporozoites. We have recently shown that IL-1alpha is produced at high levels in the liver during blood-stage P. chabaudi malaria and this cytokine is essential for inflammatory cell recruitment, pro-inflammatory cytokine production and development of hepatic necrosis. The aim of the present project is to evaluate the influence of IL-1alpha produced in the liver during blood-stage Plasmodium infection may have in a secondary liver-stage infection and its role in the protection against superinfection.

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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)
DE MENEZES, MARIA NOGUEIRA; SALLES, ERIKA MACHADO; VIEIRA, FLAVIA; AMARAL, EDUARDO PINHEIRO; ZUZARTE-LUIS, VANESSA; CASSADO, ALEXANDRA; EPIPHANIO, SABRINA; ALVAREZ, JOSE MARIA; ALVES-FILHO, JOSE CARLOS; MOTA, MARIA MANUEL; et al. IL-1 alpha, promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria. SCIENTIFIC REPORTS, v. 9, . (15/20432-8, 13/09176-4, 13/07140-2, 15/25874-9)

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