Secreted probiotic factors ameliorate enteropathogenic infection in zinc-deficient human Caco-2 and T84 cell lines.
Zinc deficiency enhances infectious diarrhea whereas probiotics may inhibit pathogen enterocyte invasion. The effect of probiotics on zinc-deficient versus normal human intestinal epithelium (Caco-2 and T-84) with regard to invasion and subsequent inflammatory response by Salmonella typhimurium was determined. Cells were infected with pathogens and preincubated with media conditioned by several lactobacilli or Bifidobacterium bifidum 12. Pathogen invasion was quantified, inflammation was determined by IL-8 secretion, and MAP kinase activation in the epithelium was analyzed. Probiotic inhibiting factors were partially characterized based on physicochemical properties. Zinc deficiency allowed for greater pathogen invasion and enhanced IL-8 secretion. Probiotic conditioned media reduced activation of proinflammatory signaling via the ERK and p38 pathway. Probiotic factors reverse increased susceptibility of zinc-deficient enterocytes to S. typhimurium invasion, suggesting an additive protective effect of probiotics in zinc deficiency. Probiotic conditioned media but not bacteria inhibited pathogen invasion and IL-8 production in zinc deficient enterocytes. Probiotic inhibitory factors are stable to treatment with proteases, deoxyribonucleases (DNAses), ribonucleases (RNAse), strong acid, and heat.
Broekaert
Ilse J
IJ
Department of Pediatrics, Mucosal Immunology and Developmental Gastroenterology Laboratories, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts 02215, USA.
Nanthakumar
N Nanda
NN
Walker
W Allan
WA
D001644:Bifidobacterium / Q000378:metabolism*; D018938:Caco-2 Cells; D017077:Culture Media, Conditioned / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007778:Lactobacillus / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D019936:Probiotics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D012260:Ribonucleases / Q000378:metabolism; D012480:Salmonella Infections / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000172:deficiency*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017077:Culture Media, Conditioned; D016209:Interleukin-8; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003851:Deoxyribonucleases; D012260:Ribonucleases; D010447:Peptide Hydrolases; D015032:Zinc