Adrenergic-mediated loss of splenic innate-like B cells contributes to infection susceptibility after stroke

Infection is a major complication and cause of mortality and morbidity after acute stroke, however the mechanisms that underlie patient susceptibility to infection are poorly understood. There are currently no proven interventions to prevent infection in stroke patients that have a beneficial impact on functional outcome and clinical trials of preventative antibiotic therapy have proven ineffective in preventing pneumonia after stroke. Splenic marginal zone (MZ) B cells are innate-like lymphocytes that provide early immunological defence against bacterial infection, in part by IgM antibody production. Experimental stroke in mice induced a marked loss of MZ B cells, deficiencies in the capture of blood-borne antigen and suppressed circulating IgM. These deficits were accompanied by susceptibility to bacterial lung infection. Circulating IgM levels were similarly suppressed in acute stroke patients and lower levels evident in patients with infection. β-adrenergic receptor antagonism prevented the loss of splenic MZ B cells in mice, preserved circulating IgM levels, and reduced bacterial burden after experimental stroke. These findings suggest that the loss of innate-like B cells mediated by adrenergic pathways contribute to the infection-prone state after stroke and identify systemic B cell dysfunction as a novel target for therapeutic manipulation.