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Characterization of effector mechanisms of innate and acquired immunity in chronic malaria model of CD28KO mice infected with Plasmodium chabaudi AS

Grant number: 09/08559-1
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): November 01, 2009
Effective date (End): April 30, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Maria Regina D'Império Lima
Grantee:Henrique Borges da Silva
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Malaria is responsible for approximately one million deaths annually, affecting mainly children. Immune system does an important role in protection against infection by Plasmodium, the causative agent of disease. Between the mechanisms involved in control of blood forms of the parasite, those mediated by antibodies appear to be fundamental. However, two recent studies developed by our research group indicate the participation of other effector mechanisms in responses against parasite. The first study shows the importance, in response against challenge, of T CD4+ memory cells produced in the course of infection; but the effector mechanisms activated by these cells are still yet to be determined. The other study delineates a possible role of innate immunity mechanisms in control of chronic parasitemia, even with a slower kinetics of action if compared to mechanisms in presence of T and B memory cells. This last study utilized mice deficient in CD28 molecule (CD28KO) infected by P. chabaudi; these mice are incapable of generate T and B memory cells and present elevated levels of chronic parasitemia which has an oscillatory pattern. In these mice, the chronic parasitemia peaks are elevated in beginning of the course of infection, and progressively diminishes with time; after 100 days of infection there are not parasites detected in circulation. This oscillatory pattern of chronic parasitemia of CD28KO mice suggests that the cells involved in innate immunity activate and deactivate redundantly with time of infection. This fact may indicate that activator and deactivator molecules are being produced in successive cycles, allowing respectively the control and recrudescence of parasitemia. Considering these results, this project was developed to characterize the effector mechanisms by which chronic parasitemia and challenge responses against P. chabaudi AS are controlled. In this way, we intend to evaluate: (1) The production of pro- and anti-inflammatory factors that could be involved in determination of oscillatory character of chronic parasitemia in CD28KO mice; (2) The effector mechanisms mediated by innate immunity involved in response to chronic parasitemia and challenge in these mice, and (3) The effects of presence of T CD4+ memory cells in immune responses against challenge by parasites, in CD28KO mice transferred with splenic T cells obtained from C57BL/6 immune mice. These objectives are concordant with previous studies that have been developed by our research group which receive financial support by FAPESP and CNPq. The intended results in this project will contribute to comprehension of mechanisms involved in immunity against malaria. (AU)

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Scientific publications (5)
(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)
DA SILVA, HENRIQUE BORGES; FONSECA, RAISSA; CASSADO, ALEXANDRA DOS ANJOS; DE SALLES, ERIKA MACHADO; DE MENEZES, MARIA NOGUEIRA; LANGHORNE, JEAN; PEREZ, KATIA REGINA; CUCCOVIA, IOLANDA MIDEA; RYFFEL, BERNHARD; BARRETO, VASCO M.; et al. In Vivo Approaches Reveal a Key Role for DCs in CD4+T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria. PLOS PATHOGENS, v. 11, n. 2, . (09/08559-1, 11/24038-1)
MOREIRA, VANESSA; TEIXEIRA, CATARINA; DA SILVA, HENRIQUE BORGES; D'IMPERIO LIMA, MARIA REGINA; DOS-SANTOS, MARIA CRISTINA. The crucial role of the MyD88 adaptor protein in the inflammatory response induced by Bothrops atrox venom. Toxicon, v. 67, p. 37-46, . (10/51150-4, 09/08559-1, 07/03337-5)
DA SILVA, HENRIQUE BORGES; DE SALLES, ERIKA MACHADO; PANATIERI, RAQUEL HOFFMANN; BOSCARDIN, SILVIA BEATRIZ; RODRIGUEZ-MALAGA, SERGIO MARCELO; ALVAREZ, JOSE MARIA; D'IMPERIO LIMA, MARIA REGINA. IFN-gamma-Induced Priming Maintains Long-Term Strain-Transcending Immunity against Blood-Stage Plasmodium chabaudi Malaria. JOURNAL OF IMMUNOLOGY, v. 191, n. 10, p. 5160-5169, . (09/08559-1, 11/24038-1)
MOREIRA, VANESSA; DOS-SANTOS, MARIA CRISTINA; NASCIMENTO, NEIDE GALVAO; DA SILVA, HENRIQUE BORGES; FERNANDES, CRISTINA MARIA; D'IMPERIO LIMA, MARIA REGINA; TEIXEIRA, CATARINA. Local inflammatory events induced by Bothrops atrox snake venom and the release of distinct classes of inflammatory mediators. Toxicon, v. 60, n. 1, p. 12-20, . (10/51150-4, 09/08559-1, 07/03337-5)
DA SILVA, HENRIQUE BORGES; DE SALLES, ERIKA MACHADO; LIMA-MAURO, ELIANA FAQUIM; SARDINHA, LUIZ ROBERTO; ALVAREZ, JOSE MARIA; D'IMPERIO LIMA, MARIA REGINA. CD28 deficiency leads to accumulation of germinal-center independent IgM(+) experienced B cells and to production of protective IgM during experimental malaria. PLoS One, v. 13, n. 8, . (10/51150-4, 15/20432-8, 09/08559-1, 13/07140-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Henrique Borges da. Effector mechanisms of the immune responses to experimental malaria.. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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