Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures.
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.
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands. r.louwen@erasmusmc.nl
Rogier
R
Louwen
Edward E S
EE
Nieuwenhuis
Leonie
L
van Marrewijk
Deborah
D
Horst-Kreft
Lilian
L
de Ruiter
Astrid P
AP
Heikema
Willem J B
WJ
van Wamel
Jaap A
JA
Wagenaar
Hubert P
HP
Endtz
Janneke
J
Samsom
Peter
P
van Baarlen
Anna
A
Akhmanova
Alex
A
van Belkum
D018988:Bacterial Translocation; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000378:metabolism; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008856:Microscopy, Fluorescence
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides