Neural targeting of Mycobacterium leprae mediated by the G domain of the laminin-alpha2 chain

Cell. 1997 Mar 21;88(6):811-21. doi: 10.1016/s0092-8674(00)81927-3.


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-alpha2 (LN-alpha2) chain on Schwann cell-axon units. Using recombinant fragments of LN-alpha2 (rLN-alpha2), the M. leprae-binding site was localized to the G domain. rLN-alpha2G mediated M. leprae binding to cell lines and to sciatic nerves of dystrophic dy/dy mice lacking LN-alpha2, but expressing laminin receptors. Anti-beta4 integrin antibody attenuated rLN-alpha2G-mediated M. leprae adherence, suggesting that M. leprae interacts with cells by binding to beta4 integrin via an LN-alpha2G 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Bacterial Adhesion / physiology
  • COS Cells / chemistry
  • COS Cells / microbiology
  • Cell Adhesion / physiology
  • Fluorescent Antibody Technique
  • Ganglia, Spinal / cytology
  • Humans
  • Integrin beta4
  • Integrins / metabolism
  • Laminin / chemistry
  • Laminin / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mycobacterium leprae / metabolism*
  • Neurons / chemistry
  • Neurons / cytology
  • Neurons / microbiology*
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Cell Surface / metabolism
  • Schwann Cells / chemistry
  • Schwann Cells / cytology
  • Schwann Cells / microbiology*
  • Sciatic Nerve / chemistry
  • Sciatic Nerve / cytology
  • Sciatic Nerve / microbiology


  • Antigens, CD
  • Integrin beta4
  • Integrins
  • Laminin
  • Receptors, Cell Surface