Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli.
Mucosal Immunol
; 8(3): 572-81, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25269707
ABSTRACT
Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NFκB signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NFκB signaling in epithelial cells through IκBα phosphorylation, NFκBp65 nuclear translocation, and TNFα secretion. In addition, NFκB activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival.
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Base de dados:
MEDLINE
Assunto principal:
Salmonella
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Doença de Crohn
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Células Epiteliais
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Evasão da Resposta Imune
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Imunidade Inata
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Mucosa Intestinal
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Macrófagos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article