title: Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model.
abstract: BACKGROUND
  Acute gastroenteritis can precipitate irritable bowel syndrome (IBS) in humans. Cytolethal distending toxin is common to all pathogens causing gastroenteritis. Its active subunit, CdtB, is associated with post-infectious bowel changes in a rat model of Campylobacter jejuni infection, including small intestinal bacterial overgrowth (SIBO).
  
  
  OBJECTIVE
  To evaluate the role of host antibodies to CdtB in contributing to post-infectious functional sequelae in this rat model.
  
  
  METHODS
  Ileal tissues from non-IBS human subjects, C. jejuni-infected and control rats were immunostained with antibodies to CdtB, c-Kit, S-100, PGP 9.5 and vinculin. Cytosolic and membrane proteins from mouse enteric neuronal cell lysates were immunoprecipitated with anti-CdtB and analyzed by mass spectrometry. ELISAs were performed on rat cardiac serum using CdtB or vinculin as antigens.
  
  
  RESULTS
  Anti-CdtB antibodies bound to a cytosolic protein in interstitial cells of Cajal (ICC) and myenteric ganglia in C. jejuni-infected and naïve rats and human subjects. Mass spectrometry identified vinculin, confirmed by co-localization and ELISAs. Anti-CdtB antibodies were higher in C. jejuni-infected rats (1.27 ± 0.15) than controls (1.76 ± 0.12) (P < 0.05), and rats that developed SIBO (2.01 ± 0.18) vs. rats that did not (1.44 ± 0.11) (P = 0.019). Vinculin expression levels were reduced in C. jejuni-infected rats (0.058 ± 0.053) versus controls (0.087 ± 0.023) (P = 0.0001), with greater reductions in rats with two C. jejuni infections (P = 0.0001) and rats that developed SIBO (P = 0.001).
  
  
  CONCLUSIONS
  Host anti-CdtB antibodies cross-react with vinculin in ICC and myenteric ganglia, required for normal gut motility. Circulating antibody levels and loss of vinculin expression correlate with number of C. jejuni exposures and SIBO, suggesting that effects on vinculin are important in the effects of C. jejuni infection on the host gut.
authors.affiliation: GI Motility Program, Division of Gastroenterology, Cedars-Sinai Medical Center, 8730 Alden Drive, Suite 225E, Los Angeles, CA, 90048, USA, mark.pimentel@cshs.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Pimentel
authors.forename: Walter
authors.initials: W
authors.lastname: Morales
authors.forename: Venkata
authors.initials: V
authors.lastname: Pokkunuri
authors.forename: Constantinos
authors.initials: C
authors.lastname: Brikos
authors.forename: Sun Moon
authors.initials: SM
authors.lastname: Kim
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Triantafyllou
authors.forename: Stacy
authors.initials: S
authors.lastname: Weitsman
authors.forename: Zachary
authors.initials: Z
authors.lastname: Marsh
authors.forename: Emily
authors.initials: E
authors.lastname: Marsh
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Chua
authors.forename: Shanthi
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Barlow
authors.forename: Christopher
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D015551:Autoimmunity; D001427:Bacterial Toxins / Q000276:immunology*; D002169:Campylobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D016123:Campylobacter jejuni / Q000276:immunology* / Q000472:pathogenicity; D003429:Cross Reactions; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000276:immunology / Q000382:microbiology; D004751:Enteritis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D005724:Ganglia / Q000276:immunology / Q000382:microbiology; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000276:immunology / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology* / Q000294:innervation / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D010641:Phenotype; D051381:Rats; D016596:Vinculin / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; C488955:VCL protein, human; C488956:Vcl protein, rat; C067044:cytolethal distending toxin; D016596:Vinculin