Syndecans promote mycobacterial internalization by lung epithelial cells

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• Pulmonary tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (Mtb).
• Alveolar epithelial cells are initial host cells for Mtb, but mechanisms of bacterial entry into these non-professional phagocytes are not fully understood.
• Understanding host-pathogen interactions at the cellular level is crucial for developing effective TB treatments.

Purpose of the Study:

• To identify host cell receptors involved in Mycobacterium tuberculosis attachment and internalization by alveolar epithelial cells.
• To elucidate the molecular mechanisms underlying the interaction between Mtb and host epithelial cells.
• To evaluate the in vivo relevance of identified receptors in a mouse model of tuberculosis.

Main Methods:

• Investigated syndecan 4 (Sdc4) expression in human and mouse alveolar epithelial cells post-Mtb infection.
• Utilized Sdc4 knockdown and antibody blocking to assess Mtb attachment and internalization.
• Analyzed molecular interactions using host syndecans (Sdc) and the Mtb heparin-binding hemagglutinin adhesin.
• Examined Mtb lung colonization in Sdc1/Sdc4 double-knockout mice.

Main Results:

• Identified syndecan 4 (Sdc4) as a key receptor for Mtb attachment to alveolar epithelial cells.
• Sdc4 mRNA expression increased upon Mtb infection.
• Sdc4 knockdown or blocking significantly reduced Mtb attachment and internalization.
• Host Sdc and Mtb heparin-binding hemagglutinin adhesin mediate the interaction.
• Sdc1/Sdc4 double-knockout mice showed reduced Mtb lung colonization.

Conclusions:

• Syndecan 4 is a critical mediator of Mtb entry into alveolar epithelial cells.
• The interaction involves specific host syndecans and Mtb adhesins.
• Targeting Sdc4 presents a potential strategy for controlling Mtb infection and TB disease progression.