Bruton's tyrosine kinase regulates Shigella flexneri dissemination in HT-29 intestinal cells.
Infect Immun
; 81(2): 598-607, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23230296
ABSTRACT
Shigella flexneri is a Gram-negative intracellular pathogen that infects the intestinal epithelium and utilizes actin-based motility to spread from cell to cell. S. flexneri actin-based motility has been characterized in various cell lines, but studies in intestinal cells are limited. Here we characterized S. flexneri actin-based motility in HT-29 intestinal cells. In agreement with studies conducted in various cell lines, we showed that S. flexneri relies on neural Wiskott-Aldrich Syndrome protein (N-WASP) in HT-29 cells. We tested the potential role of various tyrosine kinases involved in N-WASP activation and uncovered a previously unappreciated role for Bruton's tyrosine kinase (Btk) in actin tail formation in intestinal cells. We showed that Btk depletion led to a decrease in N-WASP phosphorylation which affected N-WASP recruitment to the bacterial surface, decreased the number of bacteria displaying actin-based motility, and ultimately affected the efficiency of spread from cell to cell. Finally, we showed that the levels of N-WASP phosphorylation and Btk expression were increased in response to infection, which suggests that S. flexneri infection not only triggers the production of proinflammatory factors as previously described but also manipulates cellular processes required for dissemination in intestinal cells.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Shigella flexneri
/
Proteínas Tirosina Quinases
/
Disenteria Bacilar
/
Mucosa Intestinal
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos