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Effect of staphylococcal enterotoxins type A (SEA) and B (SEB) on the neutrophil dysfunction during Staphylococcus aureus-induced sepsis

Grant number: 17/25867-8
Support Opportunities:Regular Research Grants
Duration: September 01, 2018 - February 28, 2021
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Ivani Aparecida de Souza
Grantee:Ivani Aparecida de Souza
Host Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil
Associated researchers:Edson Antunes


Sepsis is a systemic inflammatory disease which affects about 17 million people per year worldwide, with a mortality rate above 50%. It is the main cause of admission and death in the intensive care units. Brazil has a high fatality rate on public hospitals of the Brazilian Unified Health System. Sepsis by gram-positive bacteria has a higher mortality rate when compared with sepsis by gram-negative bacteria. However, experimental models that adequately mimic the signs of sepsis by gram-positive bacteria are limited. Staphylococcus aureus (S. aureus) is the main gram-positive bacteria associated with sepsis acquired in hospital settings. An inefficient neutrophils mobilization in S. aureus-induced sepsis is the main cause of death in patients infected with this bacterium. S. aureus pathological effects are due to the production and secretion of staphylococcal enterotoxins (SEs). Recently, we have shown that human eosinophils incubated with SEs exhibit reduced functional properties of chemotaxis and adhesion in response to eotaxin via MHC class II activation. A similar response was observed in mice bone marrow granulocytes. Thus, the present study aims to identify the effects of SEs on the functional properties of adhesion and chemotaxis in human neutrophils, as well as to elucidate the participation of MHC class II and the signaling pathways involved in these events. We will also investigate the effect of SEs on the expression of MAC-1 and LFA-1± adhesion molecules on the neutrophil surface. Clinical studies have revealed reduced CXCR2 receptor expression in neutrophils from patients with sepsis. Thus, we intend to further investigate the role of SEs on the expression of CXCR2 in human neutrophils. In human blood eosinophils, we will investigate the role of IFN-³ on the adhesion and chemotaxis properties of these cells. Clarifying the mechanisms by which SEs influence neutrophil and/or eosinophil functions, as well as the signaling pathways involved, may represent a significantly advantage on the development of novel and promising treatment strategies for sepsis by S. aureus. (AU)

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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)
PINHEIRO-TORRES, A. S.; FERREIRA-DUARTE, A. P.; TAKESHITA, W. M.; GUSHIKEN, V. O.; RONCALHO-BUCK, I. A.; ANHE, G. F.; ANTUNES, E.; DESOUZA, I. A.. Airways exposure of bacterial superantigen SEB enhances bone marrow eosinophil population and facilitates its egress to blood and lung tissue. Life Sciences, v. 264, . (17/15175-1, 17/25867-8)
FERREIRA-DUARTE, A. P.; PINHEIRO-TORRES, A. S.; TAKESHITA, W. M.; GUSHIKEN, V. O.; RONCALHO-BUCK, I. A.; ANHE, G. F.; DESOUZA, I. A.. Airway exposure to Staphylococcal enterotoxin type B (SEB) enhances the number and activity of bone marrow neutrophils via the release of multiple cytokines. International Immunopharmacology, v. 78, . (17/25867-8)

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