Scientific Publications by FDA Staff

Infect Immun 2008 Nov;76(11):5294-304

Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence to, Invasion into, Translocation across, and Exocytosis from Polarized Human Intestinal Caco-2 Cells.

Hu L, Tall BD, Curtis SK, Kopecko DJ

Campylobacter jejuni-mediated pathogenesis involves gut adherence and translocation across intestinal cells. The current study was undertaken to examine C. jejuni interaction with and translocation across differentiated Caco-2 cells to better understand Campylobacter's pathogenesis. C. jejuni 81-176 invasion efficiency into Caco-2 cells was reduced 2-3 fold relative to that seen with INT407 cells. Adherence/invasion analyses indicated that C. jejuni 81-176 adhered to most INT407 cells, but only invaded approximately 2/3s of host cells over 2 h (i.e. 2 bacteria/cell). In contrast, only 11-17% of differentiated Caco-2 cells were observed to bind and internalize either C. jejuni strains 81-176 or NCTC 11168, and a few percent of infected Caco-2 cells contained 5-20 internalized bacteria per cell after 2 h. EM revealed that individual C. jejuni cells adhered to the tips of host cell microvilli via intimate flagellar contacts and by lateral bacterial binding to the sides of microvilli. Next, bacteria were observed binding at the apical host membrane surface via presumed interactions at one pole of the bacterium and with host membrane protrusions located near intercellular junctions. These latter contacts apparently result in a coordinated, localized plasma membrane invagination causing simultaneous bacterial internalization into an endosome. Passage of this Campylobacter-endosome intracellularly from the apical to basolateral surface occurred over time, and bacterial release apparently resulted from endosome-basolateral membrane fusion (i.e. exocytosis). Bacteria were observed intercellularly below tight junctions at 60 min postinfection, but not at earlier times. These studies demonstrate unique host cell adherence contacts, early endocytosis-specific structures, and a presumptive exocytosis component of this transcellular transcytosis route.