Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine
Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans ( C.albicans) . Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adverse...
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| creator | Nikiforou, Maria Jacobs, Esmee M.R. Kemp, Matthew W. Hornef, Mathias W. Payne, Matthew S. Saito, Masatoshi Newnham, John P. Janssen, Leon E.W. Jobe, Alan H. Kallapur, Suhas G. Kramer, Boris W. Wolfs, Tim G.A.M. |
| description | Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (
C.albicans)
. Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic
C.albicans
infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic
C.albicans
infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic
C.albicans
infection. Pregnant sheep received intra-amniotic injections with 10
7
colony-forming units
C.albicans
or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of
C.albicans
. Intra-amniotic
C.albicans
caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3
+
lymphocytes, MPO
+
cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment
in utero
decreased intestinal
C.albicans
colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic
C.albicans
caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate
C.albicans
-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. |
| doi_str_mv | 10.1038/srep29806 |
| format | Article |
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C.albicans)
. Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic
C.albicans
infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic
C.albicans
infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic
C.albicans
infection. Pregnant sheep received intra-amniotic injections with 10
7
colony-forming units
C.albicans
or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of
C.albicans
. Intra-amniotic
C.albicans
caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3
+
lymphocytes, MPO
+
cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment
in utero
decreased intestinal
C.albicans
colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic
C.albicans
caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate
C.albicans
-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep29806</identifier><identifier>PMID: 27411776</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/21 ; 692/308/3187 ; 692/699/255/1672 ; Animals ; Antibodies ; Antifungal Agents - pharmacology ; Candida albicans - drug effects ; Candida albicans - physiology ; Candidiasis - drug therapy ; Candidiasis - microbiology ; Candidiasis - veterinary ; Chorioamnionitis - drug therapy ; Chorioamnionitis - microbiology ; Chorioamnionitis - veterinary ; Colonization ; Cytokines - genetics ; Cytokines - metabolism ; Female ; Fetus - metabolism ; Fetus - microbiology ; Fetus - pathology ; Fetuses ; Fluconazole - pharmacology ; Hospitals ; Host-Pathogen Interactions ; Humanities and Social Sciences ; Infections ; Inflammation - microbiology ; Inflammation - veterinary ; Intestinal Mucosa - embryology ; Intestinal Mucosa - microbiology ; Intestinal Mucosa - pathology ; Lymphocytes ; Microorganisms ; Morphology ; multidisciplinary ; Pregnancy ; Science ; Science (multidisciplinary) ; Sheep ; Sheep Diseases - microbiology ; Sheep Diseases - pathology ; Small intestine</subject><ispartof>Scientific reports, 2016-07, Vol.6 (1), p.29806-29806, Article 29806</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jul 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-168967e483af47f78eafcc52d258ba8209e371ff446c7e8943a3068a0d904ed13</citedby><cites>FETCH-LOGICAL-c438t-168967e483af47f78eafcc52d258ba8209e371ff446c7e8943a3068a0d904ed13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944185/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944185/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27411776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nikiforou, Maria</creatorcontrib><creatorcontrib>Jacobs, Esmee M.R.</creatorcontrib><creatorcontrib>Kemp, Matthew W.</creatorcontrib><creatorcontrib>Hornef, Mathias W.</creatorcontrib><creatorcontrib>Payne, Matthew S.</creatorcontrib><creatorcontrib>Saito, Masatoshi</creatorcontrib><creatorcontrib>Newnham, John P.</creatorcontrib><creatorcontrib>Janssen, Leon E.W.</creatorcontrib><creatorcontrib>Jobe, Alan H.</creatorcontrib><creatorcontrib>Kallapur, Suhas G.</creatorcontrib><creatorcontrib>Kramer, Boris W.</creatorcontrib><creatorcontrib>Wolfs, Tim G.A.M.</creatorcontrib><title>Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (
C.albicans)
. Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic
C.albicans
infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic
C.albicans
infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic
C.albicans
infection. Pregnant sheep received intra-amniotic injections with 10
7
colony-forming units
C.albicans
or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of
C.albicans
. Intra-amniotic
C.albicans
caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3
+
lymphocytes, MPO
+
cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment
in utero
decreased intestinal
C.albicans
colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic
C.albicans
caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate
C.albicans
-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy.</description><subject>13/21</subject><subject>692/308/3187</subject><subject>692/699/255/1672</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candida albicans - drug effects</subject><subject>Candida albicans - physiology</subject><subject>Candidiasis - drug therapy</subject><subject>Candidiasis - microbiology</subject><subject>Candidiasis - veterinary</subject><subject>Chorioamnionitis - drug therapy</subject><subject>Chorioamnionitis - microbiology</subject><subject>Chorioamnionitis - veterinary</subject><subject>Colonization</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Fetus - metabolism</subject><subject>Fetus - microbiology</subject><subject>Fetus - pathology</subject><subject>Fetuses</subject><subject>Fluconazole - pharmacology</subject><subject>Hospitals</subject><subject>Host-Pathogen Interactions</subject><subject>Humanities and Social Sciences</subject><subject>Infections</subject><subject>Inflammation - microbiology</subject><subject>Inflammation - veterinary</subject><subject>Intestinal Mucosa - embryology</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Lymphocytes</subject><subject>Microorganisms</subject><subject>Morphology</subject><subject>multidisciplinary</subject><subject>Pregnancy</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sheep</subject><subject>Sheep Diseases - microbiology</subject><subject>Sheep Diseases - pathology</subject><subject>Small intestine</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkV9rFDEUxYMottQ--AVkwBcVRvNvJsmLIIvWQsEXfQ53MzdtlplkTWYK_fZmu-uy1bzkXu4vJ-dyCHnN6EdGhf5UMm650bR_Rs45lV3LBefPT-ozclnKhtbTcSOZeUnOuJKMKdWfk3gd5wwtTDGkObhmBXEIAzQwroODWJoQPbo5pFirYXFYmmlxqcBY-82SH5r6YAeNME1w4Jr5Dpt0HyI2HudHdMYy1_4VeeFhLHh5uC_Ir29ff66-tzc_rq5XX25aJ4WeW9Zr0yuUWoCXyiuN4J3r-MA7vQbNqUGhmPdS9k6hNlKAoL0GOhgqcWDignze626X9YSDw92Wo93mMEF-sAmCfTqJ4c7epnsrjZRMd1Xg3UEgp99LNW-nUByOI0RMS7FMU6l7roWq6Nt_0E1acqzrVYqJ6s48Cr7fUy6nUjPzRzOM2l2Q9hhkZd-cuj-Sf2OrwIc9UOoo3mI--fI_tT_u06k-</recordid><startdate>20160714</startdate><enddate>20160714</enddate><creator>Nikiforou, Maria</creator><creator>Jacobs, Esmee M.R.</creator><creator>Kemp, Matthew W.</creator><creator>Hornef, Mathias W.</creator><creator>Payne, Matthew S.</creator><creator>Saito, Masatoshi</creator><creator>Newnham, John P.</creator><creator>Janssen, Leon E.W.</creator><creator>Jobe, Alan H.</creator><creator>Kallapur, Suhas G.</creator><creator>Kramer, Boris W.</creator><creator>Wolfs, Tim G.A.M.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160714</creationdate><title>Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine</title><author>Nikiforou, Maria ; Jacobs, Esmee M.R. ; Kemp, Matthew W. ; Hornef, Mathias W. ; Payne, Matthew S. ; Saito, Masatoshi ; Newnham, John P. ; Janssen, Leon E.W. ; Jobe, Alan H. ; Kallapur, Suhas G. ; Kramer, Boris W. ; Wolfs, Tim G.A.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-168967e483af47f78eafcc52d258ba8209e371ff446c7e8943a3068a0d904ed13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>13/21</topic><topic>692/308/3187</topic><topic>692/699/255/1672</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antifungal Agents - pharmacology</topic><topic>Candida albicans - drug effects</topic><topic>Candida albicans - physiology</topic><topic>Candidiasis - drug therapy</topic><topic>Candidiasis - microbiology</topic><topic>Candidiasis - veterinary</topic><topic>Chorioamnionitis - drug therapy</topic><topic>Chorioamnionitis - microbiology</topic><topic>Chorioamnionitis - veterinary</topic><topic>Colonization</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>Female</topic><topic>Fetus - metabolism</topic><topic>Fetus - microbiology</topic><topic>Fetus - pathology</topic><topic>Fetuses</topic><topic>Fluconazole - pharmacology</topic><topic>Hospitals</topic><topic>Host-Pathogen Interactions</topic><topic>Humanities and Social Sciences</topic><topic>Infections</topic><topic>Inflammation - microbiology</topic><topic>Inflammation - veterinary</topic><topic>Intestinal Mucosa - embryology</topic><topic>Intestinal Mucosa - microbiology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Lymphocytes</topic><topic>Microorganisms</topic><topic>Morphology</topic><topic>multidisciplinary</topic><topic>Pregnancy</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sheep</topic><topic>Sheep Diseases - microbiology</topic><topic>Sheep Diseases - pathology</topic><topic>Small intestine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nikiforou, Maria</creatorcontrib><creatorcontrib>Jacobs, Esmee M.R.</creatorcontrib><creatorcontrib>Kemp, Matthew W.</creatorcontrib><creatorcontrib>Hornef, Mathias W.</creatorcontrib><creatorcontrib>Payne, Matthew S.</creatorcontrib><creatorcontrib>Saito, Masatoshi</creatorcontrib><creatorcontrib>Newnham, John P.</creatorcontrib><creatorcontrib>Janssen, Leon E.W.</creatorcontrib><creatorcontrib>Jobe, Alan H.</creatorcontrib><creatorcontrib>Kallapur, Suhas G.</creatorcontrib><creatorcontrib>Kramer, Boris W.</creatorcontrib><creatorcontrib>Wolfs, Tim G.A.M.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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 One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nikiforou, Maria</au><au>Jacobs, Esmee M.R.</au><au>Kemp, Matthew W.</au><au>Hornef, Mathias W.</au><au>Payne, Matthew S.</au><au>Saito, Masatoshi</au><au>Newnham, John P.</au><au>Janssen, Leon E.W.</au><au>Jobe, Alan H.</au><au>Kallapur, Suhas G.</au><au>Kramer, Boris W.</au><au>Wolfs, Tim G.A.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-07-14</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>29806</spage><epage>29806</epage><pages>29806-29806</pages><artnum>29806</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (
C.albicans)
. Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic
C.albicans
infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic
C.albicans
infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic
C.albicans
infection. Pregnant sheep received intra-amniotic injections with 10
7
colony-forming units
C.albicans
or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of
C.albicans
. Intra-amniotic
C.albicans
caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3
+
lymphocytes, MPO
+
cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment
in utero
decreased intestinal
C.albicans
colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic
C.albicans
caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate
C.albicans
-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27411776</pmid><doi>10.1038/srep29806</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Nature Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 13/21 692/308/3187 692/699/255/1672 Animals Antibodies Antifungal Agents - pharmacology Candida albicans - drug effects Candida albicans - physiology Candidiasis - drug therapy Candidiasis - microbiology Candidiasis - veterinary Chorioamnionitis - drug therapy Chorioamnionitis - microbiology Chorioamnionitis - veterinary Colonization Cytokines - genetics Cytokines - metabolism Female Fetus - metabolism Fetus - microbiology Fetus - pathology Fetuses Fluconazole - pharmacology Hospitals Host-Pathogen Interactions Humanities and Social Sciences Infections Inflammation - microbiology Inflammation - veterinary Intestinal Mucosa - embryology Intestinal Mucosa - microbiology Intestinal Mucosa - pathology Lymphocytes Microorganisms Morphology multidisciplinary Pregnancy Science Science (multidisciplinary) Sheep Sheep Diseases - microbiology Sheep Diseases - pathology Small intestine |
| title | Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine |
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