title: Mycobacterium tuberculosis binding 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 tuberculosis has 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 of M. tuberculosis with these recognition molecules likely influence the outcome of the bacillus-host interaction. Here we use a novel fluid shear assay to investigate the binding of M. tuberculosis to 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 attenuated M. tuberculosis strains 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 attenuated M. tuberculosis strains 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 between M. tuberculosis and host innate immune determinants.
authors.affiliation: Center for Genomic Sciences, Allegheny-Singer Research Institute, 320 East North Avenue, 11th Floor, South Tower, Pittsburgh, PA 15212-4772, USA. lstoodle@wpahs.org
authors.forename: Luanne
authors.initials: L
authors.lastname: Hall-Stoodley
authors.forename: Gayle
authors.initials: G
authors.lastname: Watts
authors.forename: Joy E
authors.initials: JE
authors.lastname: Crowther
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balagopal
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.forename: James
authors.initials: J
authors.lastname: Robison-Cox
authors.forename: Robert F
authors.initials: RF
authors.lastname: Bargatze
authors.forename: Allen G
authors.initials: AG
authors.lastname: Harmsen
authors.forename: Erika C
authors.initials: EC
authors.lastname: Crouch
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
mesh_terms: D001422:Bacterial Adhesion; D001980:Bronchi / Q000382:microbiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000502:physiology*; D033081:Shear Strength
chemical_list: D005353:Fibronectins; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D