Abstract
Infection is a major complication of acute stroke and causes increased mortality and morbidity; however, current interventions do not prevent infection and improve clinical outcome in stroke patients. The mechanisms that underlie susceptibility to infection in these patients are unclear. Splenic marginal zone (MZ) B cells are innate-like lymphocytes that provide early defence against bacterial infection. Here we show experimental stroke in mice induces a marked loss of MZ B cells, deficiencies in capturing blood-borne antigen and suppression of circulating IgM. These deficits are accompanied by spontaneous bacterial lung infection. IgM levels are similarly suppressed in stroke patients. β-adrenergic receptor antagonism after experimental stroke prevents loss of splenic MZ B cells, preserves IgM levels, and reduces bacterial burden. These findings suggest that adrenergic-mediated loss of MZ B cells contributes to the infection-prone state after stroke and identify systemic B-cell disruption as a target for therapeutic manipulation.
Highlights
Infection is a major complication of acute stroke and causes increased mortality and morbidity; current interventions do not prevent infection and improve clinical outcome in stroke patients
We show that experimental stroke in mice causes rapid loss of marginal zone (MZ) B cells associated with impaired immunoglobulin M (IgM) production and spontaneous bacterial infection
middle cerebral artery occlusion (MCAO) resulted in marked disruption to the splenic microarchitecture with a loss of lymphocyte segregation and B-cell follicular structures which was consistent throughout the spleen (Fig. 1a)
Summary
Infection is a major complication of acute stroke and causes increased mortality and morbidity; current interventions do not prevent infection and improve clinical outcome in stroke patients. Given that most infections occur in the first few days after stroke, and the established role of innate-like B cells in rapid anti-bacterial defence against strains typically affecting patients, we sought to identify if systemic innate-like B-cell functions are affected by ischaemic stroke and contribute to infection susceptibility. We demonstrate lower concentrations of circulating IgM in patients with acute ischaemic stroke and that IgM levels are most suppressed in patients who develop infection Adrenergic signalling mediates these deficits, suggesting involvement of autonomic pathways in brain-immune communication affecting B-cell function after stroke. Blockade of adrenergic signalling after experimental stroke using propranolol prevents loss of MZ B cells, restores circulating IgM levels and reduces infection These data reveal loss of innate-like B-cell populations and their associated functions as an important mechanism contributing to infection susceptibility after stroke and highlight this pathway as a potential target for intervention
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