Treatment with a Urinary Bladder Matrix Alters the Innate Host Response to Pneumonia Induced by Escherichia coli.

Abstract

Escherichiacoli has become the prominent cause of nosocomial pneumonia in recent years. In the meantime, some strains of E. coli have developed resistance to commonly used antibacterial drugs. The urinary bladder matrix (UBM) is a biologically derived scaffold material that has been used to promote site-appropriate tissue remodeling in a variety of body systems, partially through the modulation of the innate immune response. In this study, we seek to determine UBM efficacy in preventing bacterial pneumonia in mouse lungs using the Gram-negative bacterial strain E. coli. Our results show that the UBM prevented bacterial biofilm formation in both abiotic and biotic conditions through experimentation on polystyrene plates and culture on the apical surface of differentiated airway epithelial cells. Intratracheal treatment with UBM led to host protection from E. coli-induced respiratory infection in a murine pneumonia model. Transcriptomic analysis revealed the involvement of the enhanced host immune response in UBM-treated mice. Additionally, UBM-treated macrophages had an increased iNOS expression and enhanced phagocytosis activity. Therefore, the protection against E. coli-induced infection and the antibacterial function observed by UBM is potentially through both the anti-biofilm activity and enhanced host immunity following UBM treatment. Taken together, our results support further investigation of UBM as an alternative treatment to attenuate bacterial-induced respiratory infection.