Symbiotic bacteria direct expression of an intestinal bactericidal lectin

The mammalian intestine harbors complex societies of beneficial bacteria that are maintained in the lumen with minimal penetration of mucosal surfaces. Microbial colonization of germ-free mice triggers epithelial expression of RegIIIγ, a secreted C-type lectin. RegIIIγ binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIγ and its human counterpart, HIP/PAP, are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host-microbial relationships. The human gut is home to a vast consortium of symbiotic bacteria. Members of this complex microflora metabolize dietary substances, such as plant polysaccharides, that are otherwise indigestible by their human hosts (1). Indigenous gut microbes thus make essential contributions to human nutrient metabolism and, in return, inhabit a protected, nutrient-rich environment. Maintaining the mutually beneficial nature of this relationship requires strict sequestration of resident bacteria in the intestinal lumen, as microbial incursions acros