Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells.
Shigella invades the human intestinal mucosa, thus causing bacillary dysentery, an acute recto-colitis responsible for lethal complications, mostly in infants and toddlers. Conversely, commensal bacteria live in a mutualistic relationship with the intestinal mucosa that is characterized by homeostatic control of innate responses, thereby contributing to tolerance to the flora. Cross-talk established between commensals and the intestinal epithelium mediate this active process, the mechanisms of which remain largely uncharacterized. Probiotics such as Lactobacillus casei belong to a subclass of these commensals that modulate mucosal innate responses and possibly display anti-inflammatory properties. We analyzed whether L. casei could attenuate the pro-inflammatory signaling induced by Shigella flexneri after invasion of the epithelial lining. Cultured epithelial cells were infected with L. casei, followed by a challenge with S. flexneri. Using macroarray DNA chips, we observed that L. casei down-regulated the transcription of a number of genes encoding pro-inflammatory effectors such as cytokines and chemokines and adherence molecules induced by invasive S. flexneri. This resulted in an anti-inflammatory effect that appeared mediated by the inhibition of the NF-kappaB pathway, particularly through stabilization of I-kappaBalpha. In a time-course experiment using GeneChip hybridization analysis, the expression of many genes involved in ubiquitination and proteasome processes were modulated during L. casei treatment. Thus, L. casei has developed a sophisticated means to maintain intestinal homeostasis through a process that involves manipulation of the ubiquitin/proteasome pathway upstream of I-kappaBalpha.
Tien
Meng-Tsung
MT
Pathogénie Microbienne Moléculaire Unit, Institut National de la Santé et de la Recherche Médicale U389, Paris, France.
Girardin
Stephen E
SE
Regnault
Béatrice
B
Le Bourhis
Lionel
L
Dillies
Marie-Agnès
MA
Coppée
Jean-Yves
JY
Bourdet-Sicard
Raphaëlle
R
Sansonetti
Philippe J
PJ
Pédron
Thierry
T
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D004247:DNA / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D007780:Lacticaseibacillus casei / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019936:Probiotics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012763:Shigella flexneri / Q000472:pathogenicity*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D016328:NF-kappa B; D025801:Ubiquitin; D004247:DNA; D046988:Proteasome Endopeptidase Complex