Cox, Eric

Devriendt, Bert

Goddeeris, Bruno

Melkebeek, Vesna

English

Ghent University Academic Bibliography

Crossing	   the	   barrier:	   targeting	   epithelial	   receptors	   for	   antigen	   delivery	   to	   the	  mucosal	  immune	  system	  	  Bert	  Devriendt,	  Vesna	  Melkebeek,	  Bruno	  Goddeeris,	  Eric	  Cox	  	  Laboratory	  of	  Immunology,	  Faculty	  of	  Veterinary	  Medicine,	  UGent,	  Merelbeke,	  Belgium	  b.devriendt@ugent.be	  	  	  The	   gastro-­‐intestinal	   immune	   system	   daily	   encounters	   a	   vast	   array	   of	   foreign	  antigens	   derived	   from	   food,	   gut-­‐residing	   commensal	   micro-­‐organisms	   and	  pathogens.	  To	  keep	  these	  innocuous	  and	  hazardous	  antigens	  at	  bay	  a	  single	  layer	  of	  epithelial	  cells,	  mostly	  enterocytes,	  lines	  the	  intestinal	  tissues.	  These	  enterocytes	  not	  only	  function	  as	  a	  barrier	  to	  prevent	  uncontrolled	  access	  of	  macromolecules	  to	  the	  subepithelial	  tissues,	  they	  also	  convey	  information	  on	  the	  gut	  luminal	  content	  to	  the	  underlying	   immune	   cells	   and	   as	   such	   enterocytes	   create	   and	   sustain	   a	   tolerogenic	  environment	  under	  steady	  state	  conditions.	  During	   infection	  however	   they	  are	  still	  able	   to	   sense	   pathogens	   and	   relay	   this	   information	   to	   induce	   an	   immunogenic	  environment,	   enabling	   antigen-­‐presenting	   cells	   (APCs)	   to	   mount	   an	   adequate	  pathogen-­‐specific	   immune	   response.	   This	   crosstalk	   between	   the	   intestinal	  epithelium	   and	   underlying	   APCs	   plays	   a	   key	   role	   in	   shaping	   the	   local	   micro-­‐environment	   towards	   tolerance	   or	   immunity.	   The	   immune	   response	   in	   the	  alimentary	  tract	  to	  soluble	  antigens	  is	  by	  default	  tolerance.	  As	  such	  oral	  vaccination	  with	  soluble	  antigens	  is	  quite	  ineffective	  to	  induce	  protective	  immunity,	  although	  a	  few	  exceptions	  exist	  such	  as	  cholera	  toxin	  (CT),	  the	  LT	  enterotoxin	  and	  colonisation	  factors	  (F4	  fimbriae)	  purified	  from	  the	  porcine-­‐specific	  pathogen	  enterotoxigenic	  E.	  coli	   (ETEC).	   Indeed,	  oral	  delivery	  of	  purified	  F4	   fimbriae	   induces	   intestinal	   immune	  responses,	  protecting	  piglets	  from	  a	  challenge	  ETEC	  infection.	  The	  polymeric	  nature	  of	  the	  fimbriae	  is	  pivotal	  for	  this	  protective	  mucosal	  immunity.	  Intriguingly,	  the	  oral	  immunogenicity	  of	   these	  antigens	   relies	  on	   their	  binding	   to	   receptors	  at	   the	  apical	  surface	  of	  enterocytes.	  We	  recently	  identified	  aminopeptidase	  N	  (APN,	  CD13)	  as	  the	  epithelial	   receptor	   involved	   in	   transcytosis	   of	   F4	   fimbriae.	   Antibody-­‐mediated	  targeting	  to	  APN	  resulted	  in	  enhanced	  epithelial	  transcytosis	  and	  promoted	  mucosal	  immune	   responses	   in	   a	   pig	   model.	   This	   ligand-­‐induced	   receptor	   activation	   seems	  necessary	  to	  switch	  the	  local	  micro-­‐environment	  from	  a	  tolerogenic	  to	  an	  immune-­‐inductive	  state.	  Thus,	  selective	  targeting	  of	  antigens	  to	  epithelial	  APN	  could	  enhance	  the	  efficacy	  of	  oral	  vaccines	  and	  accelerate	  their	  design.	  	  	  	  	  	  

Crossing the barrier: targeting epithelial receptors for antigen delivery to the mucosal immune system

https://biblio.ugent.be/publication/4146661/file/4146675

Crossing the barrier: targeting epithelial receptors for antigen delivery to the mucosal immune system

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Ghent University Academic Bibliography