Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Group A Streptococcus, A Master At Turning Its Host Against Itself (#57)

P. Patrick Cleary 1
  1. University of Minnesota, Minneapolis, MN, United States

Group A streptococci (StrepA) have evolved a variety of macromolecules that mimic their host. Autoimmune responses  to these molecules, tissue reactive antibodies, subsequent to infections are implicated in Kidney, heart and neuropathologic disorders. Mucosal infections by StrepA also induce a robust Th17 cellular response, which we showed is protective. Subsets of Th17 cells are directly involved in rodent models of autism spectrum, and multiple sclerosis, and are linked to rheumatic heart disease. The potential of these cells to migrate into the brain and spinal cord focused our research toward understanding the autoimmune neuromuscular and behavioral StrepA sequelae, Sydenham’s Chorea and Pediatric autoimmune Neurologic disorders associated with group A streptococcus (PANDAS). Although mimic antibodies, directed at brain proteins are found in sera of patients, mechanisms that allow passage of IgG into the brain are unknown. Our experiments showed that CD4 IL17+ T cells are the dominant StrepA specific helper T cell in human tonsils. A mouse model of intranasal infection combined with a MHCII Tetramers reagent revealed that StrepA specific CD4 IL17+T cells migrate from nasal associated lymphoid tissue into the olfactory bulb and other regions of the brain. Localization of T cells in the brain was accompanied by leakage of IgG across the blood brain barrier and microglial cell activation. The broader implication of these findings for exacerbations of streptococcal associated and other chronic autoimmune disorders will be considered.