A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuni.
Campylobacter jejuni is the foremost cause of bacterial-induced diarrhoeal disease worldwide. Although it is well established that C. jejuni infection of intestinal epithelia triggers host innate immune responses, the mechanism(s) involved remain poorly defined. Innate immunity can be initiated by families of structurally related pattern-recognition receptors (PRRs) that recognize specific microbial signature motifs. Here, we demonstrated maximal induction of epithelial innate responses during infection with live C. jejuni cells. In contrast when intestinal epithelial cells (IECs) were exposed to paraformaldehyde-fixed bacteria, host responses were minimal and a marked reduction in the number of intracellular bacteria was noted in parallel. These findings suggested a role for intracellular host-C. jejuni interactions in eliciting early innate immunity. We therefore investigated the potential involvement of a family of intracellular, cytoplasmic PRRs, the nucleotide-binding oligomerization domain (NOD) proteins in C. jejuni recognition. We identified NOD1, but not NOD2, as a major PRR for C. jejuni in IEC. We also found that targeting intestinal epithelial NOD1 with small interfering RNA resulted in an increase in number of intracellular C. jejuni, thus highlighting a critical role for NOD1-mediated antimicrobial defence mechanism(s) in combating this infection at the gastrointestinal mucosal surface.
Zilbauer
Matthias
M
Infectious Diseases and Microbiology Unit, Institute of Child Health, 30 Guilford St, London WC1N 1EH, UK.
Dorrell
Nick
N
Elmi
Abdi
A
Lindley
Keith J
KJ
Schüller
Stephanie
S
Jones
Hannah E
HE
Klein
Nigel J
NJ
Núnez
Gabriel
G
Wren
Brendan W
BW
Bajaj-Elliott
Mona
M
D018938:Caco-2 Cells; D016123:Campylobacter jejuni / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000502:physiology
D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein