Intestinal Granuloma Formation and Function During Yersinia pseudotuberculosis Infection- [electronic resource]
Intestinal Granuloma Formation and Function During Yersinia pseudotuberculosis Infection- [electronic resource]
- 자료유형
- 학위논문파일 국외
- 최종처리일시
- 20240214100126
- ISBN
- 9798379755959
- DDC
- 576
- 저자명
- Matsuda, Rina.
- 서명/저자
- Intestinal Granuloma Formation and Function During Yersinia pseudotuberculosis Infection - [electronic resource]
- 발행사항
- [S.l.]: : University of Pennsylvania., 2023
- 발행사항
- Ann Arbor : : ProQuest Dissertations & Theses,, 2023
- 형태사항
- 1 online resource(132 p.)
- 주기사항
- Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
- 주기사항
- Advisor: Brodsky, Igor E.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2023.
- 사용제한주기
- This item must not be sold to any third party vendors.
- 초록/해제
- 요약Granulomas are organized immune cell aggregates that form in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signaling and immune defense, inducing neutrophil-rich pyogranulomas within lymphoid tissues. However, whether pyogranulomas contribute to control of enteropathogenic Yersinia at the intestinal barrier was previously unknown. Through the work in this dissertation, we uncover that Yp triggers pyogranuloma formation within the murine intestinal mucosa. Monocyte-lineage cells were critical for granuloma-mediated control of Yp, as mice lacking circulating monocytes fail to form defined pyogranulomas and succumb to Yp infection. Yersinia lacking YopE and YopH, virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst, do not induce pyogranulomas, indicating that intestinal pyogranulomas form in response to Yp blockade of the host immune response. Mutation of YopH restores pyogranuloma formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes overcome YopH-dependent blockade of innate immune defense. Additionally, we demonstrate that the pro-inflammatory cytokine tumor necrosis factor (TNF) is required for monocyte-mediated control of Yp within intestinal pyogranulomas. We find that TNF signals in an autocrine manner to drive monocyte-intrinsic production of interleukin-1 (IL-1), which signals through IL-1 receptor on non-hematopoietic cells to enable formation of intact pyogranulomas and control of Yersinia infection. We uncover a TNF-IL-1 circuit as a crucial driver of intestinal granuloma formation and function, mechanistically defining the cellular source and target of TNF signaling that restricts intestinal Yersinia infection. Overall, this work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation. These findings increase our understanding of granuloma-mediated restriction of pathogens and may have implications for the development of therapeutics that enhance pathogen control within granulomas or suppress granulomatous inflammation in the context of autoimmune and inflammatory disease.
- 일반주제명
- Microbiology.
- 일반주제명
- Immunology.
- 일반주제명
- Cellular biology.
- 일반주제명
- Molecular biology.
- 키워드
- Granuloma
- 키워드
- Yersinia
- 기타저자
- University of Pennsylvania Cell and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 84-12B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.