Eliminating the invading extracellular and intracellular FnBp bacteria from respiratory epithelial cells by autophagy mediated through FnBp-Fn-Integrin α5β1 axis.

BACKGROUND

We previously found that the respiratory epithelial cells could eliminate the invaded (GAS) through autophagy induced by binding a fibronectin (Fn) binding protein (FnBp) expressed on the surface of GAS to plasma protein Fn and its receptor integrin α5β1 of epithelial cells. Is autophagy initiated by FnBp bacteria via FnBp-Fn-Integrin α5β1 axis a common event in respiratory epithelial cells?

METHODS

We chose () and () as representatives of extracellular and intracellular FnBp bacteria, respectively. The FnBp of them was purified and the protein function was confirmed by western blot, viable bacteria count, confocal and pull-down. The key molecule downstream of the action axis was detected by IP, mass spectrometry and bio-informatics analysis.

RESULTS

We found that different FnBp from both and could initiate autophagy through FnBp-Fn-integrin α5β1 axis and this could be considered a universal event, by which host tries to remove invading bacteria from epithelial cells. Importantly, we firstly reported that S100A8, as a key molecule downstream of integrin β1 chain, is highly expressed upon activation of integrin α5β1, which in turn up-regulates autophagy.

CONCLUSIONS

Various FnBp from FnBp bacteria have the ability to initiate autophagy via FnBp-Fn-Integrin α5β1 axis to promote the removal of invading bacteria from epithelial cells in the presence of fewer invaders. S100A8 is a key molecule downstream of Integrin α5β1 in this autophagy pathway.