Open AccessSyndecans promote mycobacterial internalization by lung epithelial cells
Author(s) -
Zimmermann Natalie,
Saiga Hiroyuki,
Houthuys Erica,
MouraAlves Pedro,
Koehler Anne,
Bandermann Silke,
Dorhoi Anca,
Kaufmann Stefan H.E.
Publication year - 2016
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12627
Subject(s) - internalization , biology , gene knockdown , respiratory tract , mycobacterium tuberculosis , microbiology and biotechnology , lung , immunology , receptor , pathology , respiratory system , tuberculosis , cell culture , medicine , biochemistry , anatomy , genetics
Summary Pulmonary tuberculosis (TB) is an airborne disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis ( Mtb ). Alveolar epithelial cells and macrophages are the first point of contact for Mtb in the respiratory tract. However, the mechanisms of mycobacterial attachment to, and internalization by, nonprofessional phagocytes, such as epithelial cells, remain incompletely understood. We identified syndecan 4 (Sdc4) as mycobacterial attachment receptor on alveolar epithelial cells. Sdc4 mRNA expression was increased in human and mouse alveolar epithelial cells after mycobacterial infection. Sdc4 knockdown in alveolar epithelial cells or blocking with anti‐Sdc4 antibody reduced mycobacterial attachment and internalization. At the molecular level, interactions between epithelial cells and mycobacteria involved host Sdc and the mycobacterial heparin‐binding hemagglutinin adhesin. In vivo , Sdc1/Sdc4 double‐knockout mice were more resistant to Mtb colonization of the lung. Our work reveals a role for distinct Sdcs in promoting mycobacterial entry into alveolar epithelial cells with impact on outcome of TB disease.