Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup B

The influence of the innate immune protein mannose-binding lectin (MBL) on the response of human phagocytes to Neisseria meningitidis was investigated. MBL increased the association of killed meningococci with neutrophils, monocytes, and macrophages by increasing the proportion of cells that recognized bacteria. MBL down-regulated the normal change in expression of the leukocyte adhesion molecules CD11b and CD62L. In an ex vivo model, the addition of MBL to the blood of MBL-deficient donors influenced the production of monocyte-derived inflammatory cytokines. The addition of high concentrations of MBL (>6 mug/mL) profoundly decreased the production of interleukin (IL)-6, IL-1 beta, and tumor necrosis factor-alpha by monocytes in response to meningococci, whereas lower concentrations enhanced the production of IL-6 and IL-1. These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease.