Investigation of high neutrophil count in peripheral blood of patients with acute Yellow Fever

• Grant number: 19/12243-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2020
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Esper Georges Kallás
• Grantee: Esper Georges Kallás
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: José Eduardo Levi

Abstract

Yellow Fever is an infectious and non-contagious disease caused by the Yellow Fever Virus (YFV), an arbovirus belonging to the Flaviviridae family. It has a broad spectrum of symptoms, ranging from asymptomatic to severe and fatal cases. Recently, a study conducted by the Laboratory of Allergy and Clinical Immunopathology, showed that absolute neutrophil count in peripheral blood was independently associated with a bad prognosis in the course of Yellow Fever disease. These findings raised new questions not only about why this association occurred but also the possible causes for this neutrophilia observed. In this context, this work aims to investigate the occurrence of intestinal microbial translocation in patients who had severe yellow fever between 2018 and 2019. To this investigation, samples of 88 patients will be analyzed for the presence of plasmatic markers of intestinal damage (I-FABP) and microbial translocation (sCD14, LBP, and EndoCAb IgM). Plasma microbioma of these samples will also be performed, which will allow the direct demonstration of microbial translocation, besides allowing to evaluate different microbial profiles associated with disease severity. In the samples obtained in 2019, a functional and phenotypic analysis will be performed, based on oxidation of dehydrorhodamine (DHR) and by the evaluation of cellular activation markers (CD66b, CD16, CD11b, CD15 and CD14), respectively, in neutrophils of patients. To date, some experimental results have already been obtained: we observed that there was no difference in the production of reactive oxygen species (ROS) among patients and healthy controls, whereas an increase in the intensity of CD66b fluorescence was observed in patients when compared to controls, demonstrating that the neutrophils of patients with yellow fever are functionally active. This results raised more attention to the possibility of microbial translocation as a cause for the increase of neutrophils in severe cases of Yellow Fever. (AU)