Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model

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). Aim 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..

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:60

Enthalten in:

Digestive diseases and sciences - 60(2014), 5 vom: 26. Nov., Seite 1195-1205

Sprache:

Englisch

Beteiligte Personen:

Pimentel, Mark [VerfasserIn]
Morales, Walter [VerfasserIn]
Pokkunuri, Venkata [VerfasserIn]
Brikos, Constantinos [VerfasserIn]
Kim, Sun Moon [VerfasserIn]
Kim, Seong Eun [VerfasserIn]
Triantafyllou, Konstantinos [VerfasserIn]
Weitsman, Stacy [VerfasserIn]
Marsh, Zachary [VerfasserIn]
Marsh, Emily [VerfasserIn]
Chua, Kathleen S. [VerfasserIn]
Srinivasan, Shanthi [VerfasserIn]
Barlow, Gillian M. [VerfasserIn]
Chang, Christopher [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

44.87$jGastroenterologie

Themen:

Cytolethal distending toxin
Irritable bowel syndrome
Small intestinal bacterial overgrowth
Vinculin

Anmerkungen:

© Springer Science+Business Media New York 2014

doi:

10.1007/s10620-014-3435-5

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC211277803X