서브메뉴
검색
Targeting Cytokines to Regulate Host Disease Tolerance to Clostridioides difficile Infection
Targeting Cytokines to Regulate Host Disease Tolerance to Clostridioides difficile Infection
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103702
- ISBN
- 9798293802036
- DDC
- 616.079
- 서명/저자
- Targeting Cytokines to Regulate Host Disease Tolerance to Clostridioides difficile Infection
- 발행사항
- [Sl] : University of Pennsylvania, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 163 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Abt, Michael C.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2025.
- 초록/해제
- 요약As the leading cause of hospital-associated infections, Clostridioides difficile is a serious public health concern. The host immune response is a major determinant of disease outcome, and previous works have identified specific components of the immune response that protect against disease or drive pathology. Cytokines are central to the regulation of the immune system and have been targeted for therapies in autoimmunity and oncology. Interleukin (IL)-22 promotes epithelial regeneration in colitis models, and previous works have shown that IL-22 is protective against C. difficile infection by enhancing complement-mediated clearance of disseminating bacteria and promoting the growth of commensal bacteria that outcompete C. difficile for nutrients. Interferon lambda (IFN-λ) plays an important role in regulating immune responses at barrier sites, and recent works have shown that it is also protective in colitis models by promoting intestinal stem cell proliferation and regulating the inflammatory response. In this dissertation, we investigated the potential for therapeutic benefit of IL-22 induction by toll-like receptor 7 (TLR7) stimulation and additionally explored the role for IFN-λ signaling in the protection against C. difficile infection. We found that oral administration of the TLR7 agonist R848 mitigated disease following C. difficile infection by stimulating the production of IL-22 from innate lymphoid cells (ILCs). This led to increased proliferation of intestinal stem cells, reducing toxin-mediated intestinal damage and limiting the systemic dissemination of C. difficile toxin. We also identified a critical role for IFN-λ signaling in regulating the immune response to C. difficile infection. Together, our results demonstrate the utility of targeting protective cytokines for immunomodulation to combat C. difficile infection.
- 일반주제명
- Immunology
- 일반주제명
- Microbiology
- 일반주제명
- Pathology
- 키워드
- Colitis models
- 키워드
- Cytokine
- 키워드
- Infection
- 키워드
- Mucosal immunity
- 기타저자
- University of Pennsylvania Cell and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008260126s2025 us c eng d■001000017358227
■00520260202103702
■006m o d
■007cr#unu||||||||
■020 ▼a9798293802036
■035 ▼a(MiAaPQ)AAI32112984
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616.079
■1001 ▼aMears, Kevin Stanton.
■24510▼aTargeting Cytokines to Regulate Host Disease Tolerance to Clostridioides difficile Infection
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a163 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Abt, Michael C.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2025.
■520 ▼aAs the leading cause of hospital-associated infections, Clostridioides difficile is a serious public health concern. The host immune response is a major determinant of disease outcome, and previous works have identified specific components of the immune response that protect against disease or drive pathology. Cytokines are central to the regulation of the immune system and have been targeted for therapies in autoimmunity and oncology. Interleukin (IL)-22 promotes epithelial regeneration in colitis models, and previous works have shown that IL-22 is protective against C. difficile infection by enhancing complement-mediated clearance of disseminating bacteria and promoting the growth of commensal bacteria that outcompete C. difficile for nutrients. Interferon lambda (IFN-λ) plays an important role in regulating immune responses at barrier sites, and recent works have shown that it is also protective in colitis models by promoting intestinal stem cell proliferation and regulating the inflammatory response. In this dissertation, we investigated the potential for therapeutic benefit of IL-22 induction by toll-like receptor 7 (TLR7) stimulation and additionally explored the role for IFN-λ signaling in the protection against C. difficile infection. We found that oral administration of the TLR7 agonist R848 mitigated disease following C. difficile infection by stimulating the production of IL-22 from innate lymphoid cells (ILCs). This led to increased proliferation of intestinal stem cells, reducing toxin-mediated intestinal damage and limiting the systemic dissemination of C. difficile toxin. We also identified a critical role for IFN-λ signaling in regulating the immune response to C. difficile infection. Together, our results demonstrate the utility of targeting protective cytokines for immunomodulation to combat C. difficile infection.
■590 ▼aSchool code: 0175.
■650 4▼aImmunology
■650 4▼aMicrobiology
■650 4▼aPathology
■653 ▼aColitis models
■653 ▼aCytokine
■653 ▼aDisease tolerance
■653 ▼aInfection
■653 ▼aMucosal immunity
■690 ▼a0982
■690 ▼a0410
■690 ▼a0571
■71020▼aUniversity of Pennsylvania▼bCell and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358227▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
