Mycobacterium tuberculosis heparin-binding haemagglutinin adhesin (HBHA) triggers receptor-mediated transcytosis without altering the integrity of tight junctions

Abstract : Mycobacterium tuberculosis, the etiologic agent of tuberculosis, adheres to, invades and multiplies in both professional phagocytes and epithelial cells. Adherence to epithelial cells is predominantly mediated by the 28-kDa heparin-binding haemagglutinin adhesin (HBHA), which is also required for the extrapulmonary dissemination of the bacilli. To study the cellular mechanisms that might result in HBHAmediated extrapulmonary dissemination, we used a transwell model of cellular barrier and fluorescence microscopy and found that HBHA induces a reorganization of the actin filament network in confluent endothelial cells, but does not affect the tight junctions that link them. When coupled to colloidal gold particles, HBHA-mediated a rapid attachment of the particles to the membrane of human laryngeal epithelial cells (non polarized HEp-2 cells) and human type II pneumocytes (polarized A-549 pneumocytes). After attachment, the particles were internalized in membrane-bound vacuoles that migrated across the polarized pneumocytes to reach the basal side. Attachment of the HBHAcoated particles was not observed when the epithelial cells were pretreated with heparinase III, a lyase that specifically cleaves the heparan sulfate chains borne by the proteoglycans. Furthermore, no binding was observed when the gold particles were coated with HBHA lacking its C-terminal heparin-binding domain. These observations indicate that HBHA induces receptor-mediated endocytosis through the recognition of heparan sulfate-containing proteoglycans by the heparin-binding domain of the adhesin. In addition, the transcellular migration of the endocytic vacuoles containing HBHA-coated particles suggests that HBHA induces epithelial transcytosis, which may represent amacrophageindependent extrapulmonary dissemination mechanism leading to systemic infection by M. tuberculosis.
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Submitted on : Friday, December 3, 2010 - 3:59:55 PM
Last modification on : Wednesday, October 9, 2019 - 1:30:10 AM

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Franco D. Menozzi, Venkata M. Reddy, Delphine Cayet, Dominique Raze, Anne-Sophie Debrie, et al.. Mycobacterium tuberculosis heparin-binding haemagglutinin adhesin (HBHA) triggers receptor-mediated transcytosis without altering the integrity of tight junctions. Microbes and Infection, Elsevier, 2006, 8 (1), pp.1-9. ⟨10.1016/j.micinf.2005.03.023⟩. ⟨hal-00542817⟩

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