Epithelial Cell Autophagy in Antibacterial Defense of the Small Intestine
Benjamin, Jamaal Louis
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The intestines of all mammals are colonized with a diverse microbiota that provide metabolic benefits to their hosts. However, this symbiotic relationship can break down when resident bacteria opportunistically invade the intestinal barrier, leading to pathologies such as inflammatory bowel disease (IBD), and bacteremia. As a result, epithelial cell innate immune responses play an essential role in preventing bacterial invasion of host tissues and maintaining a symbiotic host-bacterial relationship. Autophagy is emerging as an important component of innate immunity. Mounting evidence suggests that dysregulation of the autophagy-independent function of autophagy genes can lead to inflammatory bowel disease. However, little is known about the role of autophagy-dependent gene function in controlling interactions between intestinal bacteria and the intestinal epithelium in vivo. In this study, I have demonstrated that small intestinal epithelial cell autophagy is essential for protection against tissue invasion by intestinal pathogens and opportunistically invasive commensals. I have shown that small intestinal autophagy is an early innate immune response that functions in an epithelial cell-intrinsic MyD88-dependent, NOD2-independent manner. Utilizing mice deficient in small intestinal epithelial cell autophagy (Atg5∆IEC), I have determined that epithelial cell autophagy is required to limit pathogen dissemination to extraintestinal sites. This study thus shows that autophagy is a critical mechanism of innate immune defense that protects intestinal epithelial surfaces from bacterial invasion. My findings may lead to new insights into how autophagy protects against gastrointestinal infections and maintains homeostasis with the intestinal microbiota.