Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age
Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships bet...
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| Veröffentlicht in: | PloS one 2020-01, Vol.15 (1), p.e0224359-e0224359 |
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| creator | Fichorova, Raina N Morrison, Charles S Chen, Pai-Lien Yamamoto, Hidemi S Govender, Yashini Junaid, Damilola Ryan, Stanthia Kwok, Cynthia Chipato, Tsungai Salata, Robert A Doncel, Gustavo F |
| description | Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state. |
| doi_str_mv | 10.1371/journal.pone.0224359 |
| format | Article |
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To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0224359</identifier><identifier>PMID: 31914129</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Age ; Analysis ; Bacterial vaginosis ; Biological markers ; Biology ; Biology and Life Sciences ; Biomarkers ; Biomarkers - metabolism ; Birth control ; Breast feeding ; Breastfeeding & lactation ; Candidiasis ; Cervix ; Cervix Uteri - immunology ; Cervix Uteri - microbiology ; Cervix Uteri - pathology ; Contraceptives ; Demographics ; Dysbacteriosis ; Dysbiosis - epidemiology ; Dysbiosis - immunology ; Dysbiosis - microbiology ; Endothelial growth factors ; Endothelium ; Female ; Genital herpes ; Genital tract ; Gynecology ; Health risks ; Herpesvirus infections ; HIV ; HIV Infections - epidemiology ; HIV Infections - immunology ; HIV Infections - virology ; Human immunodeficiency virus ; Human subjects ; Humans ; IL-1β ; Immunity ; Immunity, Innate - genetics ; Infections ; Inflammation ; Innate immunity ; Intercellular adhesion molecule 1 ; Intercellular Adhesion Molecule-1 - immunology ; Intercellular Adhesion Molecule-1 - metabolism ; Interleukin 1 receptor antagonist ; Interleukin 1 Receptor Antagonist Protein - immunology ; Interleukin 1 Receptor Antagonist Protein - metabolism ; Interleukin 1 receptors ; Interleukin-1beta - immunology ; Interleukin-1beta - metabolism ; Laboratories ; Medical research ; Medical schools ; Medicine and Health Sciences ; Methods ; Microbiota ; Microbiota (Symbiotic organisms) ; Microorganisms ; Mucosa ; Mycoses ; Obstetrics ; Oxidative stress ; Oxidative Stress - immunology ; Pregnancy ; Protease inhibitors ; Proteases ; Proteinase inhibitors ; Reproductive Tract Infections - epidemiology ; Reproductive Tract Infections - immunology ; Secretory Leukocyte Peptidase Inhibitor - immunology ; Secretory Leukocyte Peptidase Inhibitor - metabolism ; Serine ; Serine proteinase ; Sexually transmitted diseases ; Sexually Transmitted Diseases - epidemiology ; Sexually Transmitted Diseases - immunology ; Sexually Transmitted Diseases - microbiology ; STD ; Thrombin ; Uganda - epidemiology ; Vagina ; Vagina - immunology ; Vagina - microbiology ; Vaginosis ; Vaginosis, Bacterial - epidemiology ; Vaginosis, Bacterial - immunology ; Vaginosis, Bacterial - microbiology ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - immunology ; Vascular Endothelial Growth Factor A - metabolism ; Women ; Zimbabwe - epidemiology</subject><ispartof>PloS one, 2020-01, Vol.15 (1), p.e0224359-e0224359</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Fichorova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Fichorova et al 2020 Fichorova et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f0a0a9d21b209df518ace3bcb8ea62cc7856fcedc6095b3dcc60d531ccf84f083</citedby><cites>FETCH-LOGICAL-c692t-f0a0a9d21b209df518ace3bcb8ea62cc7856fcedc6095b3dcc60d531ccf84f083</cites><orcidid>0000-0002-9980-5735</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948729/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948729/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31914129$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mitchell, Caroline</contributor><creatorcontrib>Fichorova, Raina N</creatorcontrib><creatorcontrib>Morrison, Charles S</creatorcontrib><creatorcontrib>Chen, Pai-Lien</creatorcontrib><creatorcontrib>Yamamoto, Hidemi S</creatorcontrib><creatorcontrib>Govender, Yashini</creatorcontrib><creatorcontrib>Junaid, Damilola</creatorcontrib><creatorcontrib>Ryan, Stanthia</creatorcontrib><creatorcontrib>Kwok, Cynthia</creatorcontrib><creatorcontrib>Chipato, Tsungai</creatorcontrib><creatorcontrib>Salata, Robert A</creatorcontrib><creatorcontrib>Doncel, Gustavo F</creatorcontrib><title>Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Analysis</subject><subject>Bacterial vaginosis</subject><subject>Biological markers</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Birth control</subject><subject>Breast feeding</subject><subject>Breastfeeding & lactation</subject><subject>Candidiasis</subject><subject>Cervix</subject><subject>Cervix Uteri - immunology</subject><subject>Cervix Uteri - microbiology</subject><subject>Cervix Uteri - pathology</subject><subject>Contraceptives</subject><subject>Demographics</subject><subject>Dysbacteriosis</subject><subject>Dysbiosis - epidemiology</subject><subject>Dysbiosis - immunology</subject><subject>Dysbiosis - microbiology</subject><subject>Endothelial growth factors</subject><subject>Endothelium</subject><subject>Female</subject><subject>Genital herpes</subject><subject>Genital tract</subject><subject>Gynecology</subject><subject>Health risks</subject><subject>Herpesvirus infections</subject><subject>HIV</subject><subject>HIV Infections - epidemiology</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - virology</subject><subject>Human immunodeficiency virus</subject><subject>Human subjects</subject><subject>Humans</subject><subject>IL-1β</subject><subject>Immunity</subject><subject>Immunity, Innate - genetics</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Intercellular adhesion molecule 1</subject><subject>Intercellular Adhesion Molecule-1 - immunology</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 Receptor Antagonist Protein - immunology</subject><subject>Interleukin 1 Receptor Antagonist Protein - metabolism</subject><subject>Interleukin 1 receptors</subject><subject>Interleukin-1beta - immunology</subject><subject>Interleukin-1beta - metabolism</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Medical schools</subject><subject>Medicine and Health Sciences</subject><subject>Methods</subject><subject>Microbiota</subject><subject>Microbiota (Symbiotic organisms)</subject><subject>Microorganisms</subject><subject>Mucosa</subject><subject>Mycoses</subject><subject>Obstetrics</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - immunology</subject><subject>Pregnancy</subject><subject>Protease inhibitors</subject><subject>Proteases</subject><subject>Proteinase inhibitors</subject><subject>Reproductive Tract Infections - epidemiology</subject><subject>Reproductive Tract Infections - immunology</subject><subject>Secretory Leukocyte Peptidase Inhibitor - immunology</subject><subject>Secretory Leukocyte Peptidase Inhibitor - metabolism</subject><subject>Serine</subject><subject>Serine proteinase</subject><subject>Sexually transmitted diseases</subject><subject>Sexually Transmitted Diseases - epidemiology</subject><subject>Sexually Transmitted Diseases - immunology</subject><subject>Sexually Transmitted Diseases - microbiology</subject><subject>STD</subject><subject>Thrombin</subject><subject>Uganda - epidemiology</subject><subject>Vagina</subject><subject>Vagina - immunology</subject><subject>Vagina - microbiology</subject><subject>Vaginosis</subject><subject>Vaginosis, Bacterial - epidemiology</subject><subject>Vaginosis, Bacterial - immunology</subject><subject>Vaginosis, Bacterial - microbiology</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - immunology</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Women</subject><subject>Zimbabwe - epidemiology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0uL2zAQx01p6W63_QalNRRKe0iql1-XQlj6CCws9HUVsjRKFGwrK8np5tLPXjnxLnHZQ_HBg_T7_2c00iTJS4zmmBb4w8b2rhPNfGs7mCNCGM2qR8k5riiZ5QTRxyfxWfLM-w1CGS3z_GlyRnGFGSbVefJnUYNzogupBLczUjSp6ToRIDVt23cm7NOtA2Vk8KntPITU6lTtfW2sNz4VnUo93PaiafZpiD6-NSGAiiYaZDBREsP0t22hG5QOts6qPu7sIBUreJ480aLx8GL8XyQ_P3_6cfl1dnX9ZXm5uJrJvCJhppFAolIE1wRVSme4FBJoLesSRE6kLMos1xKUzFGV1VTJGKiMYil1yTQq6UXy-ui7baznY-s8J5SyvCSkGIjlkVBWbPjWmVa4PbfC8MOCdSsuXDCyAU4UMFwWuUCMsZpqAUUBTOsa60LEtNHr45itr9tYFXSxNc3EdLrTmTVf2R3PK1YWpIoG70YDZ2968IG3xktoGtGB7Q91Z7jAjA11v_kHffh0I7US8QDxcmzMKwdTvsgxKjEjJI_U_AEqfgpaI-M70yauTwTvJ4LIBLgNK9F7z5ffv_0_e_1ryr49YdcgmrD2tukPD2oKsiMonfXegb5vMkZ8GJO7bvBhTPg4JlH26vSC7kV3c0H_AjjOEPo</recordid><startdate>20200108</startdate><enddate>20200108</enddate><creator>Fichorova, Raina N</creator><creator>Morrison, Charles S</creator><creator>Chen, Pai-Lien</creator><creator>Yamamoto, Hidemi S</creator><creator>Govender, Yashini</creator><creator>Junaid, Damilola</creator><creator>Ryan, Stanthia</creator><creator>Kwok, Cynthia</creator><creator>Chipato, Tsungai</creator><creator>Salata, Robert A</creator><creator>Doncel, Gustavo F</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9980-5735</orcidid></search><sort><creationdate>20200108</creationdate><title>Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age</title><author>Fichorova, Raina N ; Morrison, Charles S ; Chen, Pai-Lien ; Yamamoto, Hidemi S ; Govender, Yashini ; Junaid, Damilola ; Ryan, Stanthia ; Kwok, Cynthia ; Chipato, Tsungai ; Salata, Robert A ; Doncel, Gustavo F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f0a0a9d21b209df518ace3bcb8ea62cc7856fcedc6095b3dcc60d531ccf84f083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Analysis</topic><topic>Bacterial vaginosis</topic><topic>Biological markers</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Birth control</topic><topic>Breast feeding</topic><topic>Breastfeeding & lactation</topic><topic>Candidiasis</topic><topic>Cervix</topic><topic>Cervix Uteri - immunology</topic><topic>Cervix Uteri - microbiology</topic><topic>Cervix Uteri - pathology</topic><topic>Contraceptives</topic><topic>Demographics</topic><topic>Dysbacteriosis</topic><topic>Dysbiosis - epidemiology</topic><topic>Dysbiosis - immunology</topic><topic>Dysbiosis - microbiology</topic><topic>Endothelial growth factors</topic><topic>Endothelium</topic><topic>Female</topic><topic>Genital herpes</topic><topic>Genital tract</topic><topic>Gynecology</topic><topic>Health risks</topic><topic>Herpesvirus infections</topic><topic>HIV</topic><topic>HIV Infections - epidemiology</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - virology</topic><topic>Human immunodeficiency virus</topic><topic>Human subjects</topic><topic>Humans</topic><topic>IL-1β</topic><topic>Immunity</topic><topic>Immunity, Innate - genetics</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Innate immunity</topic><topic>Intercellular adhesion molecule 1</topic><topic>Intercellular Adhesion Molecule-1 - immunology</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Interleukin 1 receptor antagonist</topic><topic>Interleukin 1 Receptor Antagonist Protein - immunology</topic><topic>Interleukin 1 Receptor Antagonist Protein - metabolism</topic><topic>Interleukin 1 receptors</topic><topic>Interleukin-1beta - immunology</topic><topic>Interleukin-1beta - metabolism</topic><topic>Laboratories</topic><topic>Medical research</topic><topic>Medical schools</topic><topic>Medicine and Health Sciences</topic><topic>Methods</topic><topic>Microbiota</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>Microorganisms</topic><topic>Mucosa</topic><topic>Mycoses</topic><topic>Obstetrics</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - immunology</topic><topic>Pregnancy</topic><topic>Protease inhibitors</topic><topic>Proteases</topic><topic>Proteinase inhibitors</topic><topic>Reproductive Tract Infections - epidemiology</topic><topic>Reproductive Tract Infections - immunology</topic><topic>Secretory Leukocyte Peptidase Inhibitor - immunology</topic><topic>Secretory Leukocyte Peptidase Inhibitor - metabolism</topic><topic>Serine</topic><topic>Serine proteinase</topic><topic>Sexually transmitted diseases</topic><topic>Sexually Transmitted Diseases - epidemiology</topic><topic>Sexually Transmitted Diseases - immunology</topic><topic>Sexually Transmitted Diseases - microbiology</topic><topic>STD</topic><topic>Thrombin</topic><topic>Uganda - epidemiology</topic><topic>Vagina</topic><topic>Vagina - immunology</topic><topic>Vagina - microbiology</topic><topic>Vaginosis</topic><topic>Vaginosis, Bacterial - epidemiology</topic><topic>Vaginosis, Bacterial - immunology</topic><topic>Vaginosis, Bacterial - microbiology</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - immunology</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Women</topic><topic>Zimbabwe - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fichorova, Raina N</creatorcontrib><creatorcontrib>Morrison, Charles S</creatorcontrib><creatorcontrib>Chen, Pai-Lien</creatorcontrib><creatorcontrib>Yamamoto, Hidemi S</creatorcontrib><creatorcontrib>Govender, Yashini</creatorcontrib><creatorcontrib>Junaid, Damilola</creatorcontrib><creatorcontrib>Ryan, Stanthia</creatorcontrib><creatorcontrib>Kwok, Cynthia</creatorcontrib><creatorcontrib>Chipato, Tsungai</creatorcontrib><creatorcontrib>Salata, Robert A</creatorcontrib><creatorcontrib>Doncel, Gustavo F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fichorova, Raina N</au><au>Morrison, Charles S</au><au>Chen, Pai-Lien</au><au>Yamamoto, Hidemi S</au><au>Govender, Yashini</au><au>Junaid, Damilola</au><au>Ryan, Stanthia</au><au>Kwok, Cynthia</au><au>Chipato, Tsungai</au><au>Salata, Robert A</au><au>Doncel, Gustavo F</au><au>Mitchell, Caroline</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-01-08</date><risdate>2020</risdate><volume>15</volume><issue>1</issue><spage>e0224359</spage><epage>e0224359</epage><pages>e0224359-e0224359</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4-6) or high (7-10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5-4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β-to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI-to candida, lower levels of the adhesion molecule ICAM-1 -to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF-to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31914129</pmid><doi>10.1371/journal.pone.0224359</doi><tpages>e0224359</tpages><orcidid>https://orcid.org/0000-0002-9980-5735</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-01, Vol.15 (1), p.e0224359-e0224359 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2334682278 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Adult Age Analysis Bacterial vaginosis Biological markers Biology Biology and Life Sciences Biomarkers Biomarkers - metabolism Birth control Breast feeding Breastfeeding & lactation Candidiasis Cervix Cervix Uteri - immunology Cervix Uteri - microbiology Cervix Uteri - pathology Contraceptives Demographics Dysbacteriosis Dysbiosis - epidemiology Dysbiosis - immunology Dysbiosis - microbiology Endothelial growth factors Endothelium Female Genital herpes Genital tract Gynecology Health risks Herpesvirus infections HIV HIV Infections - epidemiology HIV Infections - immunology HIV Infections - virology Human immunodeficiency virus Human subjects Humans IL-1β Immunity Immunity, Innate - genetics Infections Inflammation Innate immunity Intercellular adhesion molecule 1 Intercellular Adhesion Molecule-1 - immunology Intercellular Adhesion Molecule-1 - metabolism Interleukin 1 receptor antagonist Interleukin 1 Receptor Antagonist Protein - immunology Interleukin 1 Receptor Antagonist Protein - metabolism Interleukin 1 receptors Interleukin-1beta - immunology Interleukin-1beta - metabolism Laboratories Medical research Medical schools Medicine and Health Sciences Methods Microbiota Microbiota (Symbiotic organisms) Microorganisms Mucosa Mycoses Obstetrics Oxidative stress Oxidative Stress - immunology Pregnancy Protease inhibitors Proteases Proteinase inhibitors Reproductive Tract Infections - epidemiology Reproductive Tract Infections - immunology Secretory Leukocyte Peptidase Inhibitor - immunology Secretory Leukocyte Peptidase Inhibitor - metabolism Serine Serine proteinase Sexually transmitted diseases Sexually Transmitted Diseases - epidemiology Sexually Transmitted Diseases - immunology Sexually Transmitted Diseases - microbiology STD Thrombin Uganda - epidemiology Vagina Vagina - immunology Vagina - microbiology Vaginosis Vaginosis, Bacterial - epidemiology Vaginosis, Bacterial - immunology Vaginosis, Bacterial - microbiology Vascular endothelial growth factor Vascular Endothelial Growth Factor A - immunology Vascular Endothelial Growth Factor A - metabolism Women Zimbabwe - epidemiology |
| title | Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age |
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