{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:39:23Z","timestamp":1791689963769,"version":"4.3.4"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"LSUHSC foundation"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,5,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of\n                    <jats:italic>Candida<\/jats:italic>\n                    fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H\/HeN-C57BL\/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice).\n                    <jats:italic>In vitro<\/jats:italic>\n                    designs included evaluation of\n                    <jats:italic>C.\u00a0albicans<\/jats:italic>\n                    killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1\u03b2) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1\u03b2\/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion\/neutralization of Mac-1 ligands using Mac-1\n                    <jats:sup>+\/+<\/jats:sup>\n                    PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Vaginal candidiasis, caused by\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    , affects a significant number of women worldwide. Despite an acute inflammatory response by neutrophils during infection, the response fails to reduce the organism. Instead, the response is considered a key process underlying the symptoms of vaginitis. Therefore, it is important to determine the mechanism(s) associated with the lack of vaginal neutrophil antifungal activity. The established mouse model of\n                    <jats:italic>Candida<\/jats:italic>\n                    vaginitis was used to uncover the mechanism of neutrophil dysfunction. Results revealed that heparan sulfate present in the vagina of mice susceptible to chronic vaginitis served as a competitive ligand for the receptor (Mac-1) necessary for fungal recognition and neutrophil-mediated killing. This inhibitory function of heparan sulfate, confirmed through several approaches, provides the first evidence to explain the lack of antifungal immune reactivity during vaginal candidiasis. This finding paves the way for design of therapeutic strategies to reduce\/eliminate symptomatic vaginal candidiasis and restore quality of life to those affected.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00211-17","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T20:10:33Z","timestamp":1489522233000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis"],"prefix":"10.1128","volume":"8","author":[{"given":"Junko","family":"Yano","sequence":"first","affiliation":[{"name":"Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairi C.","family":"Noverr","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"},{"name":"Department of Prosthodontics, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul L.","family":"Fidel","sequence":"additional","affiliation":[{"name":"Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, New Orleans, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.Supplement_1.S148"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199712253372607"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/14.Supplement_1.S148"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/714031126"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/168.6.1458"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.7.2403-2408.1995"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/S1064744996000439"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/3693780310001597683"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.10.5790-5799.2002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046311"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7765-7767.2005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.7081-7088.2002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2005.00212.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2041-1014.2010.00579.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01417-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00388-10"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00182-15"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00861-13"},{"key":"e_1_3_2_20_2","first-page":"668","article-title":"Major histocompatibility haplotype does not impact the course of experimentally induced murine vaginal candidiasis","volume":"49","author":"Black CA","year":"1999","unstructured":"Black CA Eyers FM Dunkley ML Clancy RL Beagley KW . 1999. 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