University of Pennsylvania researchers have explained the mechanism by which microbes invade the tissues through the epithelial cells that line the airway in a programmed and efficient manner. Researchers say that this could be a normal physiological event and the epithelial lining may not be as effective at keeping microbes out.
Furthermore, microbes that survive once past the epithelial lining tend to be pathogenic. For example, Streptococcus pneumoniae and Haemophilus influenzae are two major human pathogens causing invasive infections.
The researchers used microarray and PCR analysis of the epithelial cells' response to invasion by S. pneumoniae and H. influenzae, to find a down regulation of genes called claudins that encode proteins key to keeping the spaces between epithelial cells tight.
They observed that claudin down regulation was preceded by up regulation of another protein called SNAIL1 that suppresses claudins.
All animals recognize molecules in microbial cell walls. It was detection of these microbial molecules by host molecules called Toll-like receptors that caused the proteins responsible for keeping the cellular barrier tight to fall down on the job.
Furthermore, inhibiting claudin expression in a cell assay or stimulating the Toll-like receptors in an animal model loosened the junctions between cells and promoted bacterial movement across the epithelium.