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.
Publication types
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Antigens, Neoplasm / metabolism*
- Antigens, Neoplasm / pharmacology
- Bacteria / growth & development
- Bacteria / immunology*
- Biomarkers, Tumor / metabolism*
- Biomarkers, Tumor / pharmacology
- Chitin / metabolism
- Colony Count, Microbial
- Germ-Free Life
- Gram-Positive Bacteria / immunology
- Gram-Positive Bacteria / metabolism
- Homeostasis
- Humans
- Immunity, Innate*
- Immunity, Mucosal
- Intestine, Small / microbiology*
- Lectins, C-Type / metabolism*
- Ligands
- Listeria monocytogenes / ultrastructure
- Mice
- Oligonucleotide Array Sequence Analysis
- Pancreatitis-Associated Proteins
- Paneth Cells / immunology
- Paneth Cells / metabolism*
- Peptidoglycan / chemistry
- Peptidoglycan / metabolism*
- Protein Structure, Tertiary
- Proteins / genetics
- Proteins / metabolism*
- Proteins / pharmacology
- Recombinant Proteins / metabolism
- Secretory Vesicles / metabolism
- Symbiosis
Substances
- Antigens, Neoplasm
- Biomarkers, Tumor
- Lectins, C-Type
- Ligands
- Pancreatitis-Associated Proteins
- Peptidoglycan
- Proteins
- REG3A protein, human
- Recombinant Proteins
- Reg3g protein, mouse
- Chitin