Asunto(s)
Colon/patología , Síndrome de Ehlers-Danlos/patología , Enfermedades Linfáticas/patología , Adolescente , Anemia/complicaciones , Anemia/patología , Colonoscopía/métodos , Síndrome de Ehlers-Danlos/complicaciones , Femenino , Humanos , Hiperplasia , Enfermedades Linfáticas/complicaciones , Pérdida de PesoRESUMEN
Intestinal dendritic cells (DCs) send processes between epithelial cells into the gut lumen to sample pathogens. Noninvasive enteropathogenic Escherichia coli (EPEC) colonize the gut using a type three secretion system (T3SS) to inject effector proteins into epithelial cells. We hypothesized that EPEC might also inject proteins into DC processes to dampen immune recognition. Using a T3SS-linked fluorescence resonance energy transfer-based system we show that EPEC injects effectors into in vitro grown human myeloid DCs. Injected cells emit a blue signal due to cleavage of the green fluorescence resonance energy transfer-based substrate CCF2/AM by ß-lactamase. When cultured with a mutant EPEC unable to translocate effector proteins, myeloid DCs show rapid activation of NF-κB, secrete large amounts of proinflammatory cytokines and increase expression of CD80, CD83, and CD86, whereas wild-type EPEC barely elicits cytokine production and shuts off nuclear translocation of NF-κB p65. By deleting effector protein genes, we identified NleE as being critical for this effect. Expression of NleE in HeLa cells completely prevented nuclear p65 accumulation in response to IL1-ß, and luciferase production in an NF-κB reporter cell line. DCs cocultured with wild-type EPEC or NleE-complemented strains were less potent at inducing MLR. EPEC was also able to inject effectors into DCs sending processes through model gut epithelium in a transwell system and into Peyer's patch myeloid DCs. Thus, EPEC translocate effectors into human DCs to dampen the inflammatory response elicited by its own pathogen-associated molecular patterns.
Asunto(s)
Células Dendríticas/microbiología , Escherichia coli Enteropatógena/patogenicidad , Infecciones por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/inmunología , Factores de Virulencia/metabolismo , Western Blotting , Separación Celular , Técnicas de Cocultivo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Escherichia coli Enteropatógena/inmunología , Escherichia coli Enteropatógena/metabolismo , Ensayo de Inmunoadsorción Enzimática , Infecciones por Escherichia coli/inmunología , Proteínas de Escherichia coli/inmunología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Células HeLa , Humanos , Prueba de Cultivo Mixto de Linfocitos , Microscopía Confocal , FN-kappa B/inmunología , Factores de Virulencia/inmunologíaRESUMEN
The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Acromegalia/complicaciones , Adenoma/diagnóstico , Anastomosis Quirúrgica/efectos adversos , Colon Sigmoide/cirugía , Colonoscopía/métodos , Colonoscopía/normas , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/cirugía , Detección Precoz del Cáncer/normas , Medicina Basada en la Evidencia/métodos , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Síndromes Neoplásicos Hereditarios/diagnóstico , Vigilancia de la Población/métodos , Medicina Estatal/normas , Uréter/cirugíaRESUMEN
T cells in the Peyer's patches (PP) of the human ileum are exposed to a myriad of dietary and bacterial Ags from the gut lumen. Recall proliferative responses to common dietary Ags are readily demonstrable by PP T cells from healthy individuals, and the cytokine response is dominated by IFN-gamma. Consistent with Th1 skewing, PP cells spontaneously secrete IL-12p70, and IL-12p40 protein can be visualized underneath the PP dome epithelium. In this study, we have analyzed IL-12 signaling in PP and investigated whether IL-12 plays a functional role. CD3+ T lymphocytes isolated from PP and adjacent ileal mucosa spontaneously secrete IFN-gamma with negligible IL-4 or IL-5. RNA transcripts for IL-12Rbeta2, the signaling component of the IL-12R, are present in purified CD4+ and CD8+ T PP lymphocytes. Active STAT4, a transcription factor essential for IL-12-mediated Th1 differentiation, is readily detectable in biopsies from PP and ileal mucosa and STAT4-DNA binding activity is demonstrable by EMSA. Nuclear proteins from CD3+ T PP lymphocytes contain STAT4 and T-bet, a transcription factor selectively expressed in Th1 cells. Stimulation of freshly isolated PP cells with staphylococcal enterotoxin B dramatically enhanced the production of IFN-gamma, an effect which was largely inhibited by neutralizing anti-IL-12 Ab. These data show that IL-12 in human PP is likely to be responsible for the Th1-dominated cytokine response of the human mucosal immune system.