Mechanisms of CNS infiltration by immune cells following S. pyogenes infection

Autoimmune encephalitides (AE) are complex disorders of the central nervous system (CNS) caused by autoantibodies that recognize neuronal proteins as foreign antigens, resulting in motor disturbances, seizures and psychiatric disorders. The targets of a number of pathologic autoantibodies have been identified for AE, but little is known about how these antibodies bypass the blood-brain barrier (BBB) to cause disease. Infiltrating T cells have been identified in the brains of AE patients, but their role in disease pathogenesis is poorly understood. Group A Streptococcus (GAS) infections are known to cause autoimmune sequelae in the CNS in the form of Sydenham’s chorea (SC), which may be caused by anti-dopamine receptor autoantibodies, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS). In the Agalliu lab, Charlotte uses an animal model of SC/PANDAS to study the effects of immune cell infiltration of the CNS following multiple intranasal infections, with a specific focus on the contribution of Th17 cytokines to neuropathology and BBB dysruption.