Loss of innate-like functions of splenic marginal zone B cells after ischemic stroke and susceptibility to bacterial pneumonia

Post-stroke infection is the leading complication suffered by stroke patients leading to an increase in mortality and morbidity after stroke. Infections such as pneumonia are the most common and are typically acquired within the first three days of hospitalisation. Ischemic stroke is known to have suppressive effects on the immune system in both humans and experimental animal models. Reported post-stroke deficiencies in the adaptive immune system do not fully explain the rapid onset of infection described in the clinic. Marginal zone (MZ) B cells in the spleen provide rapid responses to bacterial infection using an antibody-mediated defence mechanism with the speed and low-specificity of the innate immune response. Individuals who lack a spleen due to congenital dysfunction or surgery are susceptible to the similar strains of encapsulated bacteria that typically cause infections in stroke patients. We have shown that experimental stroke in mice rapidly results in a disruption to splenic immune architecture and an extensive loss of lymphocytes and an ablation of MZ B cells resulting in deficiencies in the trapping of blood-borne antigen and reduced levels of circulating IgM. Spontaneous bacterial infection, correlating with the severity of brain injury, occurs in these animals. Adrenergic signalling mediates these deficits suggesting the involvement of autonomic pathways in brain-immune communication affecting systemic B cell function after stroke. These novel findings suggest that the loss of innate-like functions of B cells after stroke is an important determinant of susceptibility to infection and highlight this pathway as an important target for intervention.