NEURAL TARGETING OF MYCOBACTERIUM-LEPRAE MEDIATED BY THE G-DOMAIN OF THE LAMININ-ALPHA-2 CHAIN

We report that the molecular basis of the neural tropism of Mycobacter ium leprae is attributable to the specific binding of M. leprae to the laminin-alpha 2 (LN-alpha 2) chain on Schwann cell-axon units. Using recombinant fragments of LN-alpha 2 (rLN-alpha 2), the M. leprae-bindi ng site was localized to the G domain. rLN-alpha PG mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-alpha 2, but expressing laminin receptors. Anti-beta(4) int egrin antibody attenuated rLN-alpha 2G-mediated M. leprae adherence, s uggesting that M. leprae interacts with cells by binding to beta(4) in tegrin via an LN-alpha 2G bridge. Our results indicate a novel role fo r the G domain of LN-2 in infection and reveal a model in which a host -derived bridging molecule determines nerve tropism of a pathogen.