Paneth Cells in Intestinal Health and Disease in the Newborn

Immunologic defense mechanisms of the adaptive and innate immune systems coordinate a balance between host defense and overreaction to the proinflammatory stimuli of the resident microflora in the intestinal tract. Among cells of the intestinal innate immune system, Paneth cells, located in the small intestinal crypts of Lieberkühn, have evolved to provide immediate responses to bacteria as well as shape the composition of commensal bacterial flora in the small intestine. Paneth cells release secretory granules rich in a variety of proteins involved in host defense and inflammation, including alpha-defensins. Alpha-defensins are small, cationic peptides that exhibit a broad spectrum of antimicrobial actions. In addition, Paneth cell granules contain other antibacterial substances, including lysozyme, secretory phospholipase A2, lectins, and a variety of immunomodulatory cytokines. Paneth cell secretion is stimulated by bacteria or by components of bacterial cell envelopes, such as lipopolysaccharide and lipoteichoic acid. The number of Paneth cells, their expression of alpha-defensins, and their expression of proteins involved in the detection of luminal bacteria are reduced in fetuses compared with term newborns and adults. Hence, reduced Paneth cell numbers and immaturity in the production of antibacterial products or their ability to detect bacteria may predispose newborns, and preterm infants in particular, to pathogenic bacterial overgrowth and translocation, contributing to the development of bacteremia, sepsis, and intestinal inflammation in diseases such as necrotizing enterocolitis.