Mycobacterium tuberculosisBinding to Human Surfactant Proteins A and D, Fibronectin, and Small Airway Epithelial Cells under Shear Conditions

Abstract

A crucial step in infection is the initial attachment of a pathogen to host cells or tissue.Mycobacterium tuberculosishas evolved multiple strategies for establishing an infection within the host. The pulmonary microenvironment contains a complex milieu of pattern recognition molecules of the innate immune system that play a role in the primary response to inhaled pathogens. Encounters ofM. tuberculosiswith these recognition molecules likely influence the outcome of the bacillus-host interaction. Here we use a novel fluid shear assay to investigate the binding ofM. tuberculosisto innate immune molecules that are produced by pulmonary epithelial cells and are thought to play a role in the lung innate immune response. Virulent and attenuatedM. tuberculosisstrains bound best to immobilized human fibronectin (FN) and surfactant protein A (SP-A) under this condition. Binding under fluid shear conditions was more consistent and significant compared to binding under static conditions. Soluble FN significantly increased the adherence of both virulent and attenuatedM. tuberculosisstrains to human primary small airway epithelial cells (SAEC) under fluid shear conditions. In contrast, SP-A and SP-D effects on bacterial adherence to SAEC differed between the two strains. The use of a fluid shear model to simulate physiological conditions within the lung and select for high-affinity binding interactions should prove useful for studies that investigate interactions betweenM. tuberculosisand host innate immune determinants.