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 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.
Cash
Heather L
HL
Center for Immunology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Lora.Hooper@UTSouthwestern.edu
Whitham
Cecilia V
CV
Behrendt
Cassie L
CL
Hooper
Lora V
LV
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
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