Intestinal Epithelial Autophagy Is Essential for Host Defense against Invasive Bacteria

Benjamin JL, Sumpter R Jr, Levine B, Hooper LV. Cell Host Microbe. (2013) 13:723-34.

Speaker: Yu-ping Hong (洪羽屏)                                 Time: 15:00~16:00, Mar. 5, 2014

Commentator: Dr. Chen, Jenn-Wei (陳振暐 博士)             Place: Room 601

Abstract

    The mammalian intestine is home to a complex population of bacteria. Members of this commensal group create a mutualistic relationship with the intestinal cells. The intrinsic innate immune responses of epithelial cells are essential to limit the invasion of both commensal and pathogenic bacteria, and maintain beneficial host-bacterial relationships (1). However, little is known about the role of various cellular processes, notably autophagy, involved in regulating this process. Autophagy is an evolutionarily ancient process in which cytoplasmic materials are targeted to the lysosome for degradation. Portions of the cytoplasm are sequestered into double-membrane structures called autophagosomes that fuse with lysosomes, delivering their contents for degradation by lysosomalenzymes (2). The importance of autophagy for mammalian intestinal immunity remains underexplored. The authors demonstrated that intestinal epithelial cell autophagy can protect against tissue invasion by both opportunistically invasive commensals Enterococcus faecalis and the invasive intestinal pathogen Salmonella Typhimurium. This progress required epithelial cell intrinsic signaling via the innate immune adaptor protein MyD88. Additionally, the authors used mice with an epithelial cell-specific deletion of a critical autophagy factor to show that epithelial cell autophagy is critical for limiting extraintestinal spread of S. Typhimurium. Their findings revealed that autophagy is a key epithelial cell-autonomous mechanism of antibacterial defense that protects against dissemination of intestinal bacteria.

Reference

1.     Artis, D. (2008) Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol. 8, 411-420.

2.     Deretic, V. & Levine, B. (2009) Autophagy, immunity, and microbial adaptations. Cell Host Microbe. 5, 527-549.