This indicated that meprins can participate in modifications of the bacterial population associated with the gut mucosa. Interestingly, no decreased adhesion or invasion was observed with the enteroinvasive pathogen S. Typhimurium strain LT2 treated with meprins, probably because these bacteria use a type three secretion system to invade epithelial cells We previously reported that AIEC colonization of the intestinal mucosa is dependent on binding of type 1 pili to the glycosylated CEACAM6 receptor, which is abnormally expressed by ileal epithelial cells in CD patients. We also previously reported that flagella and outer membrane proteins via outer membrane vesicles are involved in the ability of AIEC bacteria to adhere to and to invade cultured IEC in vitro. We investigated whether meprins target these virulence factors and observed a proteolytic degradation of AIEC LF82 type 1 pili by meprins a and b, but not of flagella and OMPs. This effect was found with VE-822 active meprins but no longer observed when bacteria were treated with heat-inactivated meprins. The impaired ability of meprin-treated bacteria to adhere to and invade various intestinal epithelial cells could result from proteolytic degradation of type 1 pili. Previous molecular dissections of virulence Fingolimod factor expression in the AIEC reference strain LF82 suggested that these bacteria are highly piliated under physiological conditions in the gastrointestinal tract. Any proteolytic degradation of type 1 pili could modify the behaviour of the AIEC bacteria within the host, and any decrease in protease expression could therefore increase AIEC colonization of the ileal mucosa. AIEC infection of IECs induces the secretion of high amounts of the pro-inflammatory cytokine IL-8, a potent chemoattractant for neutrophils. We observed that when AIEC LF82 bacteria were treated by meprin a or b, IL-8 secretion by infected IECs was significantly decreased. This effect was probably due to the decrease in the ability of bacteria to adhere to and invade intestinal epithelial cells as a consequence of proteolytic degradation of type 1 pili. These results are in accordance with our previous study showing that the inflammation induced by AIEC infection of mice expressing the human CEACAM6 was not observed when the AIEC LF82 type 1 pili�Cnegative mutant was used.