Toll-like Receptors Play a crucial role in the progress of Necrotizing Enterocolitis

Necrotizing enterocolitis(NEC), the most common gastrointestinal disease and one of the major causes of high mortality and morbidity in premature infants, especially in very low and extra low birth weight premature infants, is a common difficulty seen in neonatal intensive care unit (NICU). As the immune system of neonates is immature, microbes infection becomes an important risk factor of NEC, but the detailed pathogenesis of NEC stiil remains ambiquous. Toll-like receptors(TLRs), a group of pattern recognition receptors of innate immune system, play a crucial role in recognizing pathogen-associated molecular patterns (such as lipopolysaccharide, nucleic acid of microbes, etc) and danger-associated molecular patterns (such as self DNA released from damaged cells). In addition, the signaling pathways of TLRs could activate immune inflammation cascade reaction to break the balance between pro-inflammation and anti-inflammation in gastrointestinal tract. Moreover, they also regulate the activities of enterocytes including apoptosis, migration, autophagy and proliferation, which are participated in the pathogenesis of necrotizing enterocolitis (NEC). In particularly, TLR4 as the important adaptor of intestine innate immune system is essential to the pathogenesis of this disease through the regulation of not only the production of inflammation cytokines but also various activities of intestine epithelia cells. In this review, we summarize recent studies on the role of TLRs, especially TLR4, in the intestine immunity and pathogenesis of NEC, in order to explore the novel approaches in preventing or delaying NEC progression.