Role of p38 MAP kinase and TGF-beta signaling in transepithelial migration of invasive bacterial pathogens

Beisswenger C, Coyne CB, Shchepetov M, Weiser JN
Source: J Biol Chem
Publication Date: (2007)
Issue: 282(39): 28700-8
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: human
Tissue Origin: colon
Nucleofector® I/II/2b
Streptococcus pneumoniae and Haemophilus influenzae are human pathogens that often asymptomatically colonize the mucosal surface of the upper respiratory tract, but also occasionally cause invasive disease. The ability of species to traverse the epithelium of the airway mucosa was modelled in vitro using polarized respiratory epithelial cells in culture. Migration across the epithelial barrier was preceded by loss of transepithelial resistance. Membrane products of S. pneumoniae that included lipoteichoic acid induced disruption of the epithelial barrier in a Toll-like receptor 2 dependent manner. This result correlates with a recent genetic study that associates increased TLR2 signaling with increased rates of invasive pneumococcal disease in humans. Loss of transepithelial resistance by the TLR2 ligand correlated with activation of p38 MAP kinase and TGF-ss signaling. Activation of p38 MAPK and TGF-ss signaling in epithelial cells upon nasal infection with S. pneumoniae was also demonstrated in vivo. Inhibition of either p38 MAPK or TGF-ss signaling was sufficient to inhibit the migration of S. pneumoniae or H. influenzae. Our data shows that diverse bacteria utilize common mechanisms, including MAPK and TGF-ss signaling pathways to disrupt epithelial barriers and promote invasion.