The role of inflammasomes in the phenotypic, functional and metabolic profile of astrocytes during Toxoplasma gondii infection

Abstract

The innate immune response is based on the perception of different types of molecular patterns by pattern recognition receptors, including inflammasomes. Inflammasomes are multiprotein cytosolic complexes which, when activated, lead to the production of the active form of caspase-1, a protease whose action results in the release of interleukins (IL-)1² and IL-18 and pyroptosis. Inflammasomes are mainly present in immune cells, but have been described in other cell types, such as astrocytes. Astrocytes are the most abundant cells in the central nervous system (CNS) and perform a wide variety of functions, such as assisting in the functioning of neural circuits, regulating blood flow and controlling the energy metabolism of neurons. Thus, alterations in astrocyte activity are related to the onset and progression of various diseases, both in sterile and infectious conditions. The perception of insults to the CNS by astrocytes can lead to alterations in their gene expression, metabolism and function, culminating in the appearance of reactive astrocytes. Depending on the context in which it is inserted, a reactive astrocyte can have neurotoxic or neuroprotective functions, resulting in alterations to the microenvironment and interaction with other cell types. It is already known that the inflammasomes of these cells play an important role in the course of neurological and infectious conditions, but there is a lack of data on the impact of the activation of these proteins on the metabolism and reactivity profile of astrocytes. Therefore, this study aims to identify whether inflammasomes play a role in the reactive profile and metabolic profile of an astrocyte, evaluating parameters such as cytokine release, lactate release, cell death and interaction with microglia, using classic inflammasome agonists and during infection by Toxoplasma gondii, a parasite capable of invading the CNS and causing chronic infections.