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

TitleNeural targeting of Mycobacterium leprae mediated by the G domain of the laminin-alpha2 chain.
Publication TypeJournal Article
Year of Publication1997
AuthorsRambukkana A, Salzer JL, Yurchenco PD, Tuomanen EI
Date Published1997 Mar 21
KeywordsAnimals, Antigens, CD, Bacterial Adhesion, Cell Adhesion, COS Cells, Fluorescent Antibody Technique, Ganglia, Spinal, Humans, Integrin beta4, Integrins, Laminin, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Mycobacterium leprae, Neurons, Protein Structure, Tertiary, Rats, Receptors, Cell Surface, Schwann Cells, Sciatic Nerve

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.

Alternate JournalCell
PubMed ID9118224
Grant ListAI27913 / AI / NIAID NIH HHS / United States
DK36425 / DK / NIDDK NIH HHS / United States
DK48045 / DK / NIDDK NIH HHS / United States
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