Campylobacter jejuni Translocation across Intestinal Epithelial Cells Is Facilitated by Ganglioside-Like Lipooligosaccharide Structures

R. Louwen, E.E.S. Nieuwenhuis, L. van Marrewijk, D. Horst-Kreft, L. de Ruiter, A.P. Heikema, W.J. van Wamel, J.A. Wagenaar, H.P. Endtz, J. Samsom, P. van Baarlen, A. Akhmanova, A. van Belkum

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Abstract

Translocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether sialylation of C. jejuni lipooligosaccharide (LOS) structures, generating human nerve ganglioside mimics, is important for intestinal epithelial translocation. We here show that C. jejuni isolates expressing ganglioside-like LOS bound in larger numbers to the Caco-2 intestinal epithelial cells than C. jejuni isolates lacking such structures. Next, we found that ganglioside-like LOS facilitated endocytosis of bacteria into Caco-2 cells, as visualized by quantitative microscopy using the early and late endosomal markers early endosome-associated protein 1 (EEA1), Rab5, and lysosome-associated membrane protein 1 (LAMP-1). This increased endocytosis was associated with larger numbers of surviving and translocating bacteria. Next, we found that two different intestinal epithelial cell lines (Caco-2 and T84) responded with an elevated secretion of the T-cell attractant CXCL10 to infection by ganglioside-like LOS-expressing C. jejuni isolates. We conclude that C. jejuni translocation across Caco-2 cells is facilitated by ganglioside-like LOS, which is of clinical relevance since C. jejuni ganglioside-like LOS-expressing isolates are linked with severe gastroenteritis and bloody stools in C. jejuni-infected patients.
Original languageEnglish
Pages (from-to)3307-3318
JournalInfection and Immunity
Volume80
Issue number9
DOIs
Publication statusPublished - 2012

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Keywords

  • lysosomal membrane-proteins
  • guillain-barre-syndrome
  • line caco-2
  • tight junctions
  • adherence
  • invasion
  • infection
  • oligosaccharide
  • endocytosis
  • mechanisms

Cite this

Louwen, R., Nieuwenhuis, E. E. S., van Marrewijk, L., Horst-Kreft, D., de Ruiter, L., Heikema, A. P., ... van Belkum, A. (2012). Campylobacter jejuni Translocation across Intestinal Epithelial Cells Is Facilitated by Ganglioside-Like Lipooligosaccharide Structures. Infection and Immunity, 80(9), 3307-3318. https://doi.org/10.1128/IAI.06270-11