Immunity and cognition

The central nervous system (CNS) has been long considered an immune-privileged site, underscoring the potential influence exerted by the immune system on human cognition and behavior. During last decades, the complex bidirectional communication occurring between immune cells and neurons has begun to be investigated, unveiling unexpected neuroimmune interactions shaping synaptic connections and neural network activity during both physiological and pathological conditions. Such immune modulation of cognitive abilities and behavioral responses could represent a beneficial evolutionistic protective mechanism, being required to prevent and cope with inflammatory/infectious diseases as well as to limit the potential spreading of pathogens within a close-contact community. However, when the inflammatory response becomes persistent or compartmentalized, such as during autoimmune or neuroinflammatory disorders, the overactivation of the immune system in the brain could alter the physiological function of neural networks, leading to disabling disease features like cognitive impairment, mood disorders, and altered social interactions. In this scenario, the investigation of pathological neuroimmune interactions occurring during multiple sclerosis (MS), the most frequent inflammatory neurological disorder, has significantly contributed to decipher the synaptic mechanisms potentially underlying the detrimental effects of chronic inflammation on human cognition and behavior. In this chapter, we will review the preclinical and clinical evidence pointing toward an immune-mediated disruption of synaptic plastic abilities during chronic CNS inflammation, discussing the potential molecular pathways involved in the alteration of human cognition and social skills during autoimmune inflammatory disorders.