Epithelial Innate Immune Response to Acinetobacter baumannii Challenge

Abstract

ABSTRACTCurrently,Acinetobacter baumanniiis recognized as one of the major pathogens seriously threatening our health care delivery system. Aspects of the innate immune response toA. baumanniiinfection are not yet well understood. Human β-defensins (hBDs) are epithelial cell-derived cationic antimicrobial peptides (AMPs) that also function to bridge the innate and adaptive immune system. We tested the induction of hBD-2 and -3 byA. baumanniion primary oral and skin epithelial cells and found thatA. baumanniiinduces hBD-3 transcripts to a greater extent than it induces hBD-2 transcripts on both types of cells. In addition, we found thatA. baumanniiis susceptible to hBD-2 and -3 killing at submicromolar concentrations. Moreover, hBD-3 induction byA. baumanniiwas found to be dependent on epidermal growth factor receptor (EGFR) signaling. Inhibition of mitogen-activated protein kinase resulted in reduced expression of both hBD-2 and -3. Lastly, a disintegrin and metalloprotease 17 (ADAM17; also known as TACE) was found to be critical for hBD-3 induction, while ADAM10 and dual oxidase 1 (Duox1) were not required for hBD-3 induction. Induction of AMPs is an important component of innate sensing of pathogens and may play an important role in triggering systemic immune responses toA. baumanniiinfection. Further studies on the interactions between epithelial cells andA. baumanniiwill help us understand early stages of infection and may shed light on why some individuals are more vulnerable toA. baumanniiinfection.