Perfil fenotípico das células NK em uma reexposição viral, in vitro, após uma infecção humana natural prévia pelo Vaccinia virus

Abstract

Vaccinia virus (VACV) is the causative agent of a zoonotic infection that affects cattle and humans in many regions of Brazil. Little is known about the human immunological response against VACV natural infection, but it is clear that both the innate and adaptative responses are important. It seems that the natural cytotoxicity receptors NKp30, NKp44, and NKp46 are the most important NK cell receptors for the recognition of the VACV-infected target cell. At this moment, there are few studies that analyze the profile of natural killer after a natural VACV infection. So, the present study compares the profile of NK cells in an in vitro re-exposure by Vaccinia virus (VACV), in groups that have had a previous vaccination or natural infection. A short stimulation with UV-inactivated VACV was performed. Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. However, the degranulation and secretion processes are inhibited in infected (vaccinated and unvaccinated) subjects and in the non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94, CD161 e Granzyme B in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. Furthermore, the percentage of IFN-g + NK cells was significantly lower in non-infected unvaccinated subjects, when compared with infected (vaccinated and unvaccinated) and non-infected vaccinated individuals. Our results also show that the percentage of TNF-a + NK cells was significantly higher in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals, after in vitro stimulation with UV-inactivated VACV.