Role of the inflammasomes in HIV-associated neuroinflammation and neurocognitive disorders

Abstract

HIV associated neurocognitive disorders (HAND) is a unique form of neurological impairment that stems from HIV. This disease and its characteristics can be accredited to incorporation of DNA and mRNA of HIV-1 into the CNS. A proper understanding of the intricacies of HAND and the underlying mechanisms associated with corresponding immune reactions are vital for the potential development of a reliable treatment for HAND.A common phenomenon observed in CNS cells, specifically microglia, that are infected with HAND is inflammation, which is a consequence of the activation of innate immune response due to a variety of stimuli, in this case, being the HIV infection. The CNS based inflammation is mediated by the production of cytokines, chemokines, reactive oxygen species, and secondary messengers, which occurs at CNS glia, endothelial cells and peripherally derived immune cells.Inflammasomes play a significant role with regard to neuroinflammation due to their ability to dictate the activation of various inflammatory responses. Certain stimuli can result in the activation of caspase-1; hence, leading to the processing of interleukin-1β and interleukin-18 pro-inflammatory cytokines. The processed IL-1β and IL-18 activate signaling pathways that begin the process of neuroinflammation. Due to the fact that the NLRP3 inflammasome is the most abundant in the CNS, it is the most extensively investigated inflammasome with regard to the nervous system.Due to the importance of neuroinflammation in the evolution of HAND and proliferation of neuroinflammation due to HAND, it can be concluded that there exists a relationship between HAND and inflammasomes. The aim of our review is to consolidate current knowledge of important mechanisms in HAND, specifically related to its relationship with neuroinflammation and inflammasomes to shed light on a possible improved treatment for HAND.