Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator.
Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection. Here we report that early in Shigella spp. infections, expression of the antibacterial peptides LL-37 and human beta-defensin-1 is reduced or turned off. The downregulation is detected in biopsies from patients with bacillary dysenteries and in Shigella- infected cell cultures of epithelial and monocyte origin. This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter. Analyses of bacterial molecules causing the downregulation indicate Shigella plasmid DNA as one mediator.
Islam
D
D
Laboratory Sciences Division, International Center for Diarrhoeal Disease Research, 1000 Dhaka, Bangladesh.
Bandholtz
L
L
Nilsson
J
J
Wigzell
H
H
Christensson
B
B
Agerberth
B
B
Gudmundsson
G
G
D000328:Adult; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D054804:Cathelicidins; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000378:metabolism*; D015536:Down-Regulation; D004405:Dysentery, Bacillary / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D012760:Shigella / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012761:Shigella boydii / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012762:Shigella dysenteriae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020298:U937 Cells; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D002352:Carrier Proteins; D054804:Cathelicidins; C406407:DEFB1 protein, human; D004269:DNA, Bacterial; D023083:beta-Defensins