Cerebral ischaemic stroke results in altered mucosal IgA responses and host-commensal microbiota interactions.

Stroke is a devastating neurological event with a high risk of mortality, but also results in long-term sequalae in survivors that extend beyond the central nervous system. Notably, these include gastrointestinal dysfunction and alterations in the commensal microbiota in both patients and mouse models, which have been suggested to contribute to secondary infection and poor outcome following stroke. Strikingly changes in commensal microbial community composition occur rapidly in both humans and animal models following stroke and correlate with disease severity. Despite these observations the underpinning mechanisms that drive alterations in the microbiota post-stroke remain poorly understood. The gastrointestinal tract is home to a complex network of tissue-resident immune cells that act constitutively to maintain microbial community and prevent bacterial-driven inflammation. Here we demonstrate that mice subjected to ischaemic stroke exhibit alterations in the intestinal immune system, most notably in antibody secreting B cells and the production of Immunoglobulin A (IgA) - a major effector response against commensal microbes. Mice lacking secretory IgA binding to commensal bacteria exhibit a partial reversion of stroke-induced changes in microbiota composition. Notably we also report increases in B cell and IgA-producing plasma cell frequencies in the brain and meninges following stroke. Together these findings demonstrate stroke is associated with perturbations in antibody producing immune responses both in mucosal tissues and the CNS following stroke, which in part explain stroke-induced changes in the intestinal microbiota. A mechanistic understanding of the immunological basis of stroke-associated pathologies in the periphery may open new avenues to manage the secondary complications and long-term prognosis of patients suffering from neurological disease.