Differential Susceptibility of Bacteria to Mouse Paneth Cell α-Defensins under Anaerobic Conditions.
Small intestinal Paneth cells secrete α-defensin peptides, termed cryptdins (Crps) in mice, into the intestinal lumen, where they confer immunity to oral infections and define the composition of the ileal microbiota. In these studies, facultative bacteria maintained under aerobic or anaerobic conditions displayed differential sensitivities to mouse α-defensins under in vitro assay conditions. Regardless of oxygenation, Crps 2 and 3 had robust and similar bactericidal activities againstS.Typhimurium andS. flexneri, but Crp4 activity againstS. flexneriwas attenuated in the absence of oxygen. Anaerobic bacteria varied in their susceptibility to Crps 2-4, with Crp4 showing less activity than Crps 2 and 3 againstEnterococcus faecalis, andBacteroides fragilisin anaerobic assays, butFusobacterium necrophorumwas killed only by Crp4 and not by Crps 2 and 3. The influence of anaerobiosis in modulating Crp bactericidal activities in vitro suggests that α-defensin effects on the enteric microbiota may be subject to regulation by local oxygen tension.
Department of Pathology and Laboratory Medicine, Keck School of Medicine of the University of Southern California, USC Norris Cancer Center, Los Angeles, CA 90089-9601, USA.
Jennifer R
JR
Mastroianni
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Institute of Human Virology, Baltimore, MD 21201, USA.
Wuyuan
W
Lu
Department of Pathology and Laboratory Medicine, Keck School of Medicine of the University of Southern California, USC Norris Cancer Center, Los Angeles, CA 90089-9601, USA.
Michael E
ME
Selsted
Department of Pathology and Laboratory Medicine, Keck School of Medicine of the University of Southern California, USC Norris Cancer Center, Los Angeles, CA 90089-9601, USA.
André J
AJ
Ouellette
antimicrobial peptide; cryptdin; facultative; ileum; microbicide; microbiota