Characterisation of early mucosal and neuronal lesions following Shigella flexneri infection in human colon.
BACKGROUND
Shigella, an enteroinvasive bacteria induces a major inflammatory response responsible for acute rectocolitis in humans. However, early effect of Shigella flexneri (S. flexneri) infection upon the human mucosa and its microenvironement, in particular the enteric nervous system, remains currently unknown. Therefore, in this study, we sought to characterize ex vivo the early events of shigellosis in a model of human colonic explants. In particular, we aimed at identifying factors produced by S. flexneri and responsible for the lesions of the barrier. We also aimed at determining the putative lesions of the enteric nervous system induced by S. flexneri.


RESULTS
We first showed that, following 3 h of infection, the invasive but not the non-invasive strain of S. flexneri induced significant desquamation of the intestinal epithelial barrier and a reduction of epithelial height. These changes were significantly reduced following infection with SepA deficient S. flexneri strains. Secondly, S. flexneri induced rapid neuronal morphological alterations suggestive of cell death in enteric submucosal neurones. These alterations were associated with a significant increase in the proportion of vasoactive intestinal peptide (VIP) immunoreactive (IR) neurons but not in total VIP levels. The NMDA receptor antagonist MK-801 blocked neuronal morphological changes induced by S. flexneri, but not the increase in the proportion of VIP-IR.


CONCLUSIONS
This human explant model can be used to gain better insight into the early pathogenic events following S. flexneri infection and the mechanisms involved.
Coron
Emmanuel
E
INSERM, U913, Nantes, France.
Flamant
Mathurin
M
Aubert
Philippe
P
Wedel
Thilo
T
Pedron
Thierry
T
Letessier
Eric
E
Galmiche
Jean P
JP
Sansonetti
Philippe J
PJ
Neunlist
Michel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003108:Colonic Diseases / Q000382:microbiology* / Q000473:pathology; D004405:Dysentery, Bacillary / Q000382:microbiology* / Q000473:pathology*; D017615:Enteric Nervous System / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D012763:Shigella flexneri; D014660:Vasoactive Intestinal Peptide; D055815:Young Adult
D014660:Vasoactive Intestinal Peptide