title: Symbiotic bacteria direct expression of an intestinal bactericidal lectin.
abstract: 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 RegIIIgamma, a secreted C-type lectin. RegIIIgamma binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We show that RegIIIgamma 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.
authors.affiliation: Center for Immunology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Lora.Hooper@UTSouthwestern.edu
authors.forename: Heather L
authors.initials: HL
authors.lastname: Cash
authors.forename: Cecilia V
authors.initials: CV
authors.lastname: Whitham
authors.forename: Cassie L
authors.initials: CL
authors.lastname: Behrendt
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000494:pharmacology; D002686:Chitin / Q000378:metabolism; D015169:Colony Count, Microbial; D005856:Germ-Free Life; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007421:Intestine, Small / Q000382:microbiology*; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008089:Listeria monocytogenes / Q000648:ultrastructure; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D000073718:Pancreatitis-Associated Proteins; D019879:Paneth Cells / Q000276:immunology / Q000378:metabolism*; D010457:Peptidoglycan / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D013559:Symbiosis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D008024:Ligands; D000073718:Pancreatitis-Associated Proteins; D010457:Peptidoglycan; D011506:Proteins; C000612141:REG3A protein, human; D011994:Recombinant Proteins; C490255:Reg3g protein, mouse; D002686:Chitin