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, incl...
Gespeichert in:
| Veröffentlicht in: | Digestive diseases and sciences 2015-05, Vol.60 (5), p.1195-1205 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1205 |
|---|---|
| container_issue | 5 |
| container_start_page | 1195 |
| container_title | Digestive diseases and sciences |
| container_volume | 60 |
| creator | Pimentel, Mark Morales, Walter Pokkunuri, Venkata Brikos, Constantinos Kim, Sun Moon Kim, Seong Eun Triantafyllou, Konstantinos Weitsman, Stacy Marsh, Zachary Marsh, Emily Chua, Kathleen S. Srinivasan, Shanthi Barlow, Gillian M. Chang, Christopher |
| description | 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
|
| doi_str_mv | 10.1007/s10620-014-3435-5 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1680755140</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712943967</galeid><sourcerecordid>A712943967</sourcerecordid><originalsourceid>FETCH-LOGICAL-c509t-50982f5677ef677eb23f46c1bd9ef3f81f745550dcd67970c81e26adee338e453</originalsourceid><addsrcrecordid>eNp1kt2O1CAUxxujccfVB_DGkHjjTVegBdrLceLoJmM0Rr0lDD3MMFIYC82mL-EzS-36GQ3JgXB-__ORc4riMcFXBGPxPBLMKS4xqcuqrljJ7hQrwkRVUsabu8UKE57fhPCL4kGMJ4xxKwi_X1xQVtOaYroqvq7HFGzfj96mCe2s_xzRJ-v16KxHKaB0BPROpWM4H6dogwuHCQWDNscheKvRdvQ62eCVQy_CDbjsUP4AEW2Dc-HG-gPaqP48ubBXOsGATnDKqdC1N_BdiHIahd6rhN6EDtzD4p5RLsKj2_uy-Lh9-WHzuty9fXW9We9KzXCbymwaahgXAsxs9rQyNddk37VgKtMQI2rGGO50x0UrsG4IUK46gKpqoGbVZfFsiXsewpcRYpK9jRqcUx7CGCXhDRaMkRpn9Olf6CmMQ-54oUgupea_qINyIK03IQ1Kz0HlWhDa1lXLRaau_kHl00FvdfBgbP7_Q0AWgR5CjAMYeR5sr4ZJEiznHZDLDsi8A3LeATn39uS24HHfQ_dT8WPoGaALELMrT2v4raP_Rv0GSK-7wA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1680109846</pqid></control><display><type>article</type><title>Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Pimentel, Mark ; Morales, Walter ; Pokkunuri, Venkata ; Brikos, Constantinos ; Kim, Sun Moon ; Kim, Seong Eun ; Triantafyllou, Konstantinos ; Weitsman, Stacy ; Marsh, Zachary ; Marsh, Emily ; Chua, Kathleen S. ; Srinivasan, Shanthi ; Barlow, Gillian M. ; Chang, Christopher</creator><creatorcontrib>Pimentel, Mark ; Morales, Walter ; Pokkunuri, Venkata ; Brikos, Constantinos ; Kim, Sun Moon ; Kim, Seong Eun ; Triantafyllou, Konstantinos ; Weitsman, Stacy ; Marsh, Zachary ; Marsh, Emily ; Chua, Kathleen S. ; Srinivasan, Shanthi ; Barlow, Gillian M. ; Chang, Christopher</creatorcontrib><description>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.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-014-3435-5</identifier><identifier>PMID: 25424202</identifier><identifier>CODEN: DDSCDJ</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antibodies ; Antibodies, Bacterial - immunology ; Autoimmunity ; Bacterial Toxins - immunology ; Biochemistry ; Campylobacter Infections - immunology ; Campylobacter Infections - microbiology ; Campylobacter Infections - physiopathology ; Campylobacter jejuni - immunology ; Campylobacter jejuni - pathogenicity ; Cross Reactions ; Disease Models, Animal ; Enteric Nervous System - immunology ; Enteric Nervous System - microbiology ; Enteritis - immunology ; Enteritis - microbiology ; Enteritis - physiopathology ; Ganglia - immunology ; Ganglia - microbiology ; Gastroenteritis ; Gastroenterology ; Health aspects ; Hepatology ; Humans ; Infection ; Interstitial Cells of Cajal - immunology ; Interstitial Cells of Cajal - microbiology ; Intestine, Small - immunology ; Intestine, Small - innervation ; Intestine, Small - microbiology ; Intestine, Small - physiopathology ; Irritable bowel syndrome ; Mass spectrometry ; Medicine ; Medicine & Public Health ; Membrane proteins ; Mice ; Oncology ; Original Article ; Phenotype ; Protein binding ; Rats ; Transplant Surgery ; Vinculin - immunology ; Viral antibodies</subject><ispartof>Digestive diseases and sciences, 2015-05, Vol.60 (5), p.1195-1205</ispartof><rights>Springer Science+Business Media New York 2014</rights><rights>COPYRIGHT 2015 Springer</rights><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-50982f5677ef677eb23f46c1bd9ef3f81f745550dcd67970c81e26adee338e453</citedby><cites>FETCH-LOGICAL-c509t-50982f5677ef677eb23f46c1bd9ef3f81f745550dcd67970c81e26adee338e453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-014-3435-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-014-3435-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25424202$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pimentel, Mark</creatorcontrib><creatorcontrib>Morales, Walter</creatorcontrib><creatorcontrib>Pokkunuri, Venkata</creatorcontrib><creatorcontrib>Brikos, Constantinos</creatorcontrib><creatorcontrib>Kim, Sun Moon</creatorcontrib><creatorcontrib>Kim, Seong Eun</creatorcontrib><creatorcontrib>Triantafyllou, Konstantinos</creatorcontrib><creatorcontrib>Weitsman, Stacy</creatorcontrib><creatorcontrib>Marsh, Zachary</creatorcontrib><creatorcontrib>Marsh, Emily</creatorcontrib><creatorcontrib>Chua, Kathleen S.</creatorcontrib><creatorcontrib>Srinivasan, Shanthi</creatorcontrib><creatorcontrib>Barlow, Gillian M.</creatorcontrib><creatorcontrib>Chang, Christopher</creatorcontrib><title>Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>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.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Bacterial - immunology</subject><subject>Autoimmunity</subject><subject>Bacterial Toxins - immunology</subject><subject>Biochemistry</subject><subject>Campylobacter Infections - immunology</subject><subject>Campylobacter Infections - microbiology</subject><subject>Campylobacter Infections - physiopathology</subject><subject>Campylobacter jejuni - immunology</subject><subject>Campylobacter jejuni - pathogenicity</subject><subject>Cross Reactions</subject><subject>Disease Models, Animal</subject><subject>Enteric Nervous System - immunology</subject><subject>Enteric Nervous System - microbiology</subject><subject>Enteritis - immunology</subject><subject>Enteritis - microbiology</subject><subject>Enteritis - physiopathology</subject><subject>Ganglia - immunology</subject><subject>Ganglia - microbiology</subject><subject>Gastroenteritis</subject><subject>Gastroenterology</subject><subject>Health aspects</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Infection</subject><subject>Interstitial Cells of Cajal - immunology</subject><subject>Interstitial Cells of Cajal - microbiology</subject><subject>Intestine, Small - immunology</subject><subject>Intestine, Small - innervation</subject><subject>Intestine, Small - microbiology</subject><subject>Intestine, Small - physiopathology</subject><subject>Irritable bowel syndrome</subject><subject>Mass spectrometry</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Membrane proteins</subject><subject>Mice</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Protein binding</subject><subject>Rats</subject><subject>Transplant Surgery</subject><subject>Vinculin - immunology</subject><subject>Viral antibodies</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kt2O1CAUxxujccfVB_DGkHjjTVegBdrLceLoJmM0Rr0lDD3MMFIYC82mL-EzS-36GQ3JgXB-__ORc4riMcFXBGPxPBLMKS4xqcuqrljJ7hQrwkRVUsabu8UKE57fhPCL4kGMJ4xxKwi_X1xQVtOaYroqvq7HFGzfj96mCe2s_xzRJ-v16KxHKaB0BPROpWM4H6dogwuHCQWDNscheKvRdvQ62eCVQy_CDbjsUP4AEW2Dc-HG-gPaqP48ubBXOsGATnDKqdC1N_BdiHIahd6rhN6EDtzD4p5RLsKj2_uy-Lh9-WHzuty9fXW9We9KzXCbymwaahgXAsxs9rQyNddk37VgKtMQI2rGGO50x0UrsG4IUK46gKpqoGbVZfFsiXsewpcRYpK9jRqcUx7CGCXhDRaMkRpn9Olf6CmMQ-54oUgupea_qINyIK03IQ1Kz0HlWhDa1lXLRaau_kHl00FvdfBgbP7_Q0AWgR5CjAMYeR5sr4ZJEiznHZDLDsi8A3LeATn39uS24HHfQ_dT8WPoGaALELMrT2v4raP_Rv0GSK-7wA</recordid><startdate>20150501</startdate><enddate>20150501</enddate><creator>Pimentel, Mark</creator><creator>Morales, Walter</creator><creator>Pokkunuri, Venkata</creator><creator>Brikos, Constantinos</creator><creator>Kim, Sun Moon</creator><creator>Kim, Seong Eun</creator><creator>Triantafyllou, Konstantinos</creator><creator>Weitsman, Stacy</creator><creator>Marsh, Zachary</creator><creator>Marsh, Emily</creator><creator>Chua, Kathleen S.</creator><creator>Srinivasan, Shanthi</creator><creator>Barlow, Gillian M.</creator><creator>Chang, Christopher</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150501</creationdate><title>Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model</title><author>Pimentel, Mark ; Morales, Walter ; Pokkunuri, Venkata ; Brikos, Constantinos ; Kim, Sun Moon ; Kim, Seong Eun ; Triantafyllou, Konstantinos ; Weitsman, Stacy ; Marsh, Zachary ; Marsh, Emily ; Chua, Kathleen S. ; Srinivasan, Shanthi ; Barlow, Gillian M. ; Chang, Christopher</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c509t-50982f5677ef677eb23f46c1bd9ef3f81f745550dcd67970c81e26adee338e453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Bacterial - immunology</topic><topic>Autoimmunity</topic><topic>Bacterial Toxins - immunology</topic><topic>Biochemistry</topic><topic>Campylobacter Infections - immunology</topic><topic>Campylobacter Infections - microbiology</topic><topic>Campylobacter Infections - physiopathology</topic><topic>Campylobacter jejuni - immunology</topic><topic>Campylobacter jejuni - pathogenicity</topic><topic>Cross Reactions</topic><topic>Disease Models, Animal</topic><topic>Enteric Nervous System - immunology</topic><topic>Enteric Nervous System - microbiology</topic><topic>Enteritis - immunology</topic><topic>Enteritis - microbiology</topic><topic>Enteritis - physiopathology</topic><topic>Ganglia - immunology</topic><topic>Ganglia - microbiology</topic><topic>Gastroenteritis</topic><topic>Gastroenterology</topic><topic>Health aspects</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Infection</topic><topic>Interstitial Cells of Cajal - immunology</topic><topic>Interstitial Cells of Cajal - microbiology</topic><topic>Intestine, Small - immunology</topic><topic>Intestine, Small - innervation</topic><topic>Intestine, Small - microbiology</topic><topic>Intestine, Small - physiopathology</topic><topic>Irritable bowel syndrome</topic><topic>Mass spectrometry</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Membrane proteins</topic><topic>Mice</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Phenotype</topic><topic>Protein binding</topic><topic>Rats</topic><topic>Transplant Surgery</topic><topic>Vinculin - immunology</topic><topic>Viral antibodies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pimentel, Mark</creatorcontrib><creatorcontrib>Morales, Walter</creatorcontrib><creatorcontrib>Pokkunuri, Venkata</creatorcontrib><creatorcontrib>Brikos, Constantinos</creatorcontrib><creatorcontrib>Kim, Sun Moon</creatorcontrib><creatorcontrib>Kim, Seong Eun</creatorcontrib><creatorcontrib>Triantafyllou, Konstantinos</creatorcontrib><creatorcontrib>Weitsman, Stacy</creatorcontrib><creatorcontrib>Marsh, Zachary</creatorcontrib><creatorcontrib>Marsh, Emily</creatorcontrib><creatorcontrib>Chua, Kathleen S.</creatorcontrib><creatorcontrib>Srinivasan, Shanthi</creatorcontrib><creatorcontrib>Barlow, Gillian M.</creatorcontrib><creatorcontrib>Chang, Christopher</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pimentel, Mark</au><au>Morales, Walter</au><au>Pokkunuri, Venkata</au><au>Brikos, Constantinos</au><au>Kim, Sun Moon</au><au>Kim, Seong Eun</au><au>Triantafyllou, Konstantinos</au><au>Weitsman, Stacy</au><au>Marsh, Zachary</au><au>Marsh, Emily</au><au>Chua, Kathleen S.</au><au>Srinivasan, Shanthi</au><au>Barlow, Gillian M.</au><au>Chang, Christopher</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>60</volume><issue>5</issue><spage>1195</spage><epage>1205</epage><pages>1195-1205</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><coden>DDSCDJ</coden><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).
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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>25424202</pmid><doi>10.1007/s10620-014-3435-5</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0163-2116 |
| ispartof | Digestive diseases and sciences, 2015-05, Vol.60 (5), p.1195-1205 |
| issn | 0163-2116 1573-2568 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1680755140 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Animals Antibodies Antibodies, Bacterial - immunology Autoimmunity Bacterial Toxins - immunology Biochemistry Campylobacter Infections - immunology Campylobacter Infections - microbiology Campylobacter Infections - physiopathology Campylobacter jejuni - immunology Campylobacter jejuni - pathogenicity Cross Reactions Disease Models, Animal Enteric Nervous System - immunology Enteric Nervous System - microbiology Enteritis - immunology Enteritis - microbiology Enteritis - physiopathology Ganglia - immunology Ganglia - microbiology Gastroenteritis Gastroenterology Health aspects Hepatology Humans Infection Interstitial Cells of Cajal - immunology Interstitial Cells of Cajal - microbiology Intestine, Small - immunology Intestine, Small - innervation Intestine, Small - microbiology Intestine, Small - physiopathology Irritable bowel syndrome Mass spectrometry Medicine Medicine & Public Health Membrane proteins Mice Oncology Original Article Phenotype Protein binding Rats Transplant Surgery Vinculin - immunology Viral antibodies |
| title | Autoimmunity Links Vinculin to the Pathophysiology of Chronic Functional Bowel Changes Following Campylobacter jejuni Infection in a Rat Model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T15%3A39%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Autoimmunity%20Links%20Vinculin%20to%20the%20Pathophysiology%20of%20Chronic%20Functional%20Bowel%20Changes%20Following%20Campylobacter%20jejuni%20Infection%20in%20a%20Rat%20Model&rft.jtitle=Digestive%20diseases%20and%20sciences&rft.au=Pimentel,%20Mark&rft.date=2015-05-01&rft.volume=60&rft.issue=5&rft.spage=1195&rft.epage=1205&rft.pages=1195-1205&rft.issn=0163-2116&rft.eissn=1573-2568&rft.coden=DDSCDJ&rft_id=info:doi/10.1007/s10620-014-3435-5&rft_dat=%3Cgale_proqu%3EA712943967%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1680109846&rft_id=info:pmid/25424202&rft_galeid=A712943967&rfr_iscdi=true |