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The Contribution of Cervicovaginal Microbiota and Hormonal Contraceptives to Genital Inflammation and HIV Acquisition Risk- [electronic resource]
The Contribution of Cervicovaginal Microbiota and Hormonal Contraceptives to Genital Inflammation and HIV Acquisition Risk- [electronic resource]
상세정보
- 자료유형
- 학위논문(국외)
- 자관 청구기호
- 기본표목-개인명
- 표제와 책임표시사항
- The Contribution of Cervicovaginal Microbiota and Hormonal Contraceptives to Genital Inflammation and HIV Acquisition Risk - [electronic resource] / Anahtar, Melis Nuray.
- 발행, 배포, 간사 사항
- 형태사항
- 1 online resource(168 p)
- 일반주기
- Source: Dissertation Abstracts International, Volume: 77-04(E), Section: B.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2015.
- 이용제한주기
- This item is not available from ProQuest Dissertations & Theses.
- 요약 등 주기
- 요약The HIV epidemic persists in many parts of the world, with the majority of new infections occurring through the female genital tract (FGT). The permissiveness of the genital mucosa to HIV is modulated by the integrity of the epithelial barrier, the presence of pro-inflammatory cytokines, and the frequency of CCR5+CD4+ T cell targets. Here we focus on two biological perturbations: endogenous alterations in cervicovaginal bacteria and exogenous injectable progestin-only contraceptives (IPCs). We examine their effects on the genital mucosal environment and their link to HIV susceptibility in a cohort of young South African women.
- 요약 등 주기
- 요약We first sought to determine how genital microbiota modulate host inflammatory responses. The existing paradigm is that vaginal monocolonization by Lactobacillus is normal, and encroachment by other bacteria is pathologic. By characterizing cervicovaginal bacterial communities in 94 South African women using 16S rRNA and shotgun sequencing, we found that the majority of participants had low Lactobacillus abundance and high ecological diversity. One diverse Prevotella-containing community type strongly correlated with increased concentrations of multiple genital pro-inflammatory cytokines in vivo. We found that these cytokines were produced by epithelial cells and antigen presenting cells via different bacterial sensing mechanisms. Our results identify specific bacterial species that alter the inflammatory state of the FGT and may more broadly impact reproductive health in women.
- 요약 등 주기
- 요약We also investigated the immunological effects of IPCs, the most common form of birth control in sub-Saharan Africa. Although highly effective as a contraceptive, IPCs are controversially associated with increased HIV susceptibility by an unclear mechanism. We found that IPC users had a 5.5-fold higher risk of acquiring HIV than women not using family planning (p=0.0031, 95% CI: 1.733 -- 16.80). Phenotypic cellular analysis revealed that IPC users also had a significantly higher frequency of activated HIV target cells in the cervix. Since the availability of target cells in the genital mucosa enables early viral replication, recruitment or retention of these cells by IPCs may explain the observed increased HIV acquisition rates. Furthermore, IPC use was not associated with differences in genital cytokine levels, indicating that cervicovaginal bacteria and exogenous progesterone increase HIV susceptibility by unique pathways.
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 부출표목-단체명
- 기본자료저록
- Dissertation Abstracts International. 77-04B(E).
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 원문정보보기
- 소장사항
-
20170404 2017
MARC
008170601s2015 us esm 001c eng■001MOKWON01255789
■00520170418121653
■007cr
■020 ▼a9781339291604
■035 ▼a(MiAaPQ)AAI3738681
■040 ▼aMiAaPQ▼cMiAaPQ
■090 ▼a전자도서(박사논문)
■1001 ▼aAnahtar, Melis Nuray.
■24514▼aThe Contribution of Cervicovaginal Microbiota and Hormonal Contraceptives to Genital Inflammation and HIV Acquisition Risk▼h[electronic resource]▼cAnahtar, Melis Nuray.
■260 ▼a[Sl]▼bHarvard University▼c2015
■300 ▼a1 online resource(168 p)
■500 ▼aSource: Dissertation Abstracts International, Volume: 77-04(E), Section: B.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2015.
■506 ▼aThis item is not available from ProQuest Dissertations & Theses.
■520 ▼aThe HIV epidemic persists in many parts of the world, with the majority of new infections occurring through the female genital tract (FGT). The permissiveness of the genital mucosa to HIV is modulated by the integrity of the epithelial barrier, the presence of pro-inflammatory cytokines, and the frequency of CCR5+CD4+ T cell targets. Here we focus on two biological perturbations: endogenous alterations in cervicovaginal bacteria and exogenous injectable progestin-only contraceptives (IPCs). We examine their effects on the genital mucosal environment and their link to HIV susceptibility in a cohort of young South African women.
■520 ▼aWe first sought to determine how genital microbiota modulate host inflammatory responses. The existing paradigm is that vaginal monocolonization by Lactobacillus is normal, and encroachment by other bacteria is pathologic. By characterizing cervicovaginal bacterial communities in 94 South African women using 16S rRNA and shotgun sequencing, we found that the majority of participants had low Lactobacillus abundance and high ecological diversity. One diverse Prevotella-containing community type strongly correlated with increased concentrations of multiple genital pro-inflammatory cytokines in vivo. We found that these cytokines were produced by epithelial cells and antigen presenting cells via different bacterial sensing mechanisms. Our results identify specific bacterial species that alter the inflammatory state of the FGT and may more broadly impact reproductive health in women.
■520 ▼aWe also investigated the immunological effects of IPCs, the most common form of birth control in sub-Saharan Africa. Although highly effective as a contraceptive, IPCs are controversially associated with increased HIV susceptibility by an unclear mechanism. We found that IPC users had a 5.5-fold higher risk of acquiring HIV than women not using family planning (p=0.0031, 95% CI: 1.733 -- 16.80). Phenotypic cellular analysis revealed that IPC users also had a significantly higher frequency of activated HIV target cells in the cervix. Since the availability of target cells in the genital mucosa enables early viral replication, recruitment or retention of these cells by IPCs may explain the observed increased HIV acquisition rates. Furthermore, IPC use was not associated with differences in genital cytokine levels, indicating that cervicovaginal bacteria and exogenous progesterone increase HIV susceptibility by unique pathways.
■590 ▼aSchool code: 0084.
■650 4▼aImmunology
■650 4▼aMicrobiology
■690 ▼a0982
■690 ▼a0410
■71020▼aHarvard University▼bMedical Sciences.
■7730 ▼tDissertation Abstracts International▼g77-04B(E).
■773 ▼tDissertation Abstract International
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2015
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T14491590▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a20170404▼f2017
