The role of the neutrophils in the progression of invasive pulmonary aspergillosis in a murine model, for different samples of Aspergillus fumigatus

• Grant number: 09/07889-8
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2009
• End date: December 31, 2011
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Claudia Maria Leite Maffei
• Grantee: Claudia Maria Leite Maffei
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Invasive Pulmonary Aspergillosis (IPA) is an opportunist fungi disease caused mainly by Aspergillus fumigatus (90-95% of the cases) that attacks immunocompromised patients and represents a serious issue for the contemporary medicine. Studies have been shown that in experimental models, the pulmonary response against Aspergillus fumigatus differs in agreement with the immunosuppressive regime used, which affects the germination of conidia, and it induces or not a dependent response of influx of PMN (polymorphonuclear cells). However it should also be evaluated in those models the role of the virulence of the samples of this fungi. In that way, the main goal of this project is to evaluate the role of the neutrophils during the evolution of the IPA induced in immunocompromised mice treated with antibodies anti-granulocytes (Ly-6G / GR-1) and infected with three different Aspergillus fumigates samples. For this purpose, the fungal samples obtained of patients observed in the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HC-FMRP) and characterized as for the elastase production (virulence factor), will be inoculated intratracheally, in mice depleted of neutrophils by treatment with antibodies anti-granulocytes (Ly-6G / GR-1). The animals will be sacrificed in different times after inoculation (6, 12, 24, 48 and 72 hours), their lungs will be removed and bronchoalveolar lavage (BAL) will be collected. With those materials will be evaluated: the cellular type recruited to the place of the infection; the index of alveolous-capillary lesion caused during the infection established by the hemoglobin concentration in BAL; the adhesion process of the fungi to the inflammatory cells for analysis in Transmission Electronic Microscopy; the curve of survival of the animals infected with the different samples of the fungi and the quantification of fungi in the lung, by account of the Colony-Forming Units (CFU). (AU)