Neural targeting of Mycobacterium leprae mediated by the G domain of the laminin-α2 chain

Anura Rambukkana, James L. Salzer, Peter D. Yurchenco, Elaine I. Tuomanen

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

We report that the molecular basis of the neural tropism of Mycobacterium leprae is attributable to the specific binding of M. leprae to the laminin-α2 (LN-α2) chain on Schwann cell-axon units. Using recombinant fragments of LN-α2 (rLN-α2), the M. leprae-binding site was localized to the G domain. rLN-α2G mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-α2, but expressing laminin receptors. Anti-β4 integrin antibody attenuated rLN-α2G-mediated M. leprae adherence, suggesting that M. leprae interacts with cells by binding to β4 integrin via an LN-α2G bridge. Our results indicate a novel role for 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.

Original languageEnglish (US)
Pages (from-to)811-821
Number of pages11
JournalCell
Volume88
Issue number6
DOIs
StatePublished - Mar 21 1997

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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