Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis

Background: pneumococcal meningitis is the most common and severe form of bacterial meningitis. fatality rates are substantial,and long-term sequelae develop in about half of survivors. disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. the complement system,which mediates key inflammatory processes,has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. methods: we investigated mannose-binding lectin-associated serine protease (masp-2) levels in cerebrospinal fluid (csf) samples derived from the diagnostic lumbar puncture,which was available for 307 of 792 pneumococcal meningitis episodes included in our prospective nationwide cohort study (39%),and the association between these levels and clinical outcome. subsequently,we studied the role of masp-2 in our experimental pneumococcal meningitis mouse model using masp2 -/- mice and evaluated the potential of adjuvant treatment with masp-2-specific monoclonal antibodies in wild-type (wt) mice. results: masp-2 levels in cerebrospinal fluid of patients with bacterial meningitis were correlated with poor functional outcome. consistent with these human data,masp2-deficient mice with pneumococcal meningitis had lower cytokine levels and increased survival compared to wt mice. adjuvant treatment with masp-2-specific monoclonal antibodies led to reduced complement activation and decreased disease severity. conclusions: masp-2 contributes to poor disease outcome in human and mice with pneumococcal meningitis. masp-2-specific monoclonal antibodies can be used to attenuate the inflammatory response in pneumococcal meningitis. © 2016 the author(s).