TY - JOUR
T1 - Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model
AU - Pimentel, Mark
AU - Morales, Walter
AU - Pokkunuri, Venkata
AU - Brikos, Constantinos
AU - Kim, Sun Moon
AU - Kim, Seong Eun
AU - Triantafyllou, Konstantinos
AU - Weitsman, Stacy
AU - Marsh, Zachary
AU - Marsh, Emily
AU - Chua, Kathleen S.
AU - Srinivasan, Shanthi
AU - Barlow, Gillian M.
AU - Chang, Christopher
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Cytolethal distending toxin
KW - Irritable bowel syndrome
KW - Small intestinal bacterial overgrowth
KW - Vinculin
UR - http://www.scopus.com/inward/record.url?scp=84937965074&partnerID=8YFLogxK
U2 - 10.1007/s10620-014-3435-5
DO - 10.1007/s10620-014-3435-5
M3 - Article
C2 - 25424202
AN - SCOPUS:84937965074
SN - 0163-2116
VL - 60
SP - 1195
EP - 1205
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 5
ER -