Caracterização da resposta imune citocínica na infecção humana pelo vírus oropouche e sua relação com o padrão de soroconversão e a presença de sintomas

Abstract

This thesis is the first global study that researches and analyzes the immune response of cytokine in human infections by Orthobunyavirus Oropuche virus. The study used 320 samples of human serum. Sixty were from the Blood Bank (negative control) and 260 were obtained from two outbreaks of the Oropouche virus in the State of Pará and Amapá (Brazil). The latter was divided into 8 subgroups for better data accuracy. The collected samples were analyzed for clinical data/symptoms with serologic testing by titration of antibodies by the hemagglutination inhibition (IgM/IgG) and the detection cytokines plasma levels by flow cytometry. This allowed for the technical description of cytokine. The data obtained allowed for the observation of the characteristics and the behavior of the cytokines signatures expressed by patients by the presence or not of the virus. This also allowed for the observation of changes to serum through the presence of specific symptoms such as fever, chills, headache and dizziness. This led to the following conclusions a) there is a pattern in the synthesis of pro-inflammatory and regulatory cytokines; b) there is a balance in the profile of the immune response between pro-inflammatory cytokines (Th1) and modulators (Th17); c) an infection by the Oropouche virus alters the production of cytokines in individuals; d) the results also show that whem comparing individuals no responders with early responders, there was an increase of IL-1β and decreased IL- 12; no responders with late responders, there was a decrease of IL-8, and increased IFN-α, IL-23 and IL-17; No responders occurred early responders compared with the increase IL-4 and IFN-g; However, when compared early responders and late responders, decreased IFN-α and IL-6; early responders generally showed a decrease in IL-10 and late responders showed an increase in IL-5; e) The results also show the expression of IL-5 in patients who showed symptoms specific for Oropouche infection (fever, chills, headache and dizziness), suggesting this signal to be directly associated with pathogenesis of the virus; f) there is a need to complement this research with more studies such as those related to the expression of chemokines.