A role for Fibroblast Growth Factor Receptor 1 in the pathogenesis of Neisseria meningitidis

Abstract

Neisseria meningitidis remains an important cause of human disease. It is highly adapted to the human host - its only known reservoir. Adaptations to the host environment include many specific interactions with human molecules including iron-binding proteins, components of the innate and adaptive immune systems, and cell surface receptors such as the Epidermal Growth Factor Receptor (EGFR). Interaction of the meningococcus with EGFR has been elucidated in some detail and leads to intracellular signalling and cytoskeletal changes contributing to the pathogenesis of the organism. Here, we show that the meningococcus also recruits Fibroblast Growth Factor Receptor 1 (FGFR1) onto the surface of human blood microvascular epithelial cells (HBMECs). Furthermore, meningococci internalised into these cells recruit the activated form of this receptor, and that expression and activation of FGFR1 is necessary for efficient internalisation of meningococci into HBMECs. We show that Neisseria meningitidis interacts specifically with the IIIc isoform of FGFR1.