Avaliação dos efeitos do complexo ZIKV+IgG+ sobre células microgliais murinas

Abstract

After the epidemic of the Zika virus (ZIKV) in Brazil, infection with this pathogen was associated with damage to the central nervous system (CNS) and congenital anomalies. The adaptations and genetic mutations acquired by this virus, the result of its migration across the continents, make the effects caused by it more severe when we talk about CNS and the congenital Zika syndrome (SCZ), due to its ability to cross the placenta. and reach brain tissue. This mechanism results in severe neurological changes by inducing neuroinflammation, microglial activation and secreted neurotoxic factors. After being infected, the fetus develops lesions that can compromise its structure in formation, because ZIKV triggers an insufficient immune response in the fetus that has only the protection of maternal antibodies, of the class Immunoglobulin G (IgG), recognized for providing passive immune response and for be the only one able to cross the placenta. Due to limited knowledge about the late consequences of ZIKV infection and the role of maternal antibodies for the fetus, the aim of this work was to evaluate the role of the ZIKV+IgG complex in murine microglia cells in order to investigate its influence on adhesion and viability of these cells, as well as their involvement in oxidative stress and mitochondrial homeostasis. For this, the cells were exposed for 24 and 72 hours to ZIKV, IgG antibodies and the ZIKV+IgG complex. The cytotoxic effects of exposure to treatments were assessed by the cell viability assay (MTT). The oxidative stress relationship was assessed using the exposure test with DCFHDA and the mitochondrial membrane potential was measured using the JC-1 fluorescence assay. The results showed that IgG antibodies are cytotoxic to microglia, both alone and in the presence of ZIKV, impairing the viability of these cells, altering the potential of mitochondrial membrane and inducing the production of oxidative damage. With this work we conclude that IgG antibodies are harmful to microglia, as they induce their activation and are capable of interfering in the production of a neurotoxic environment, which can promote oxidative stress and imbalance in mitochondrial homeostasis. Therefore, we can infer that these factors may be related to the increased potential for ZIKV neuroinflammation with severe long-term consequences for CNS.