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Investigating The Role of The Human NAIP/NLRC4 Inflammasome in Host Defense Against Gram-Negative Bacterial Infection
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Investigating The Role of The Human NAIP/NLRC4 Inflammasome in Host Defense Against Gram-Negative Bacterial Infection. |
| 개인저자 | Reyes Ruiz, Valeria M. |
| 단체저자명 | University of Pennsylvania. Cell and Molecular Biology. |
| 발행사항 | [S.l.]: University of Pennsylvania., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 154 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781088383667 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Shin, Sunny. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Inflammasomes are key multiprotein intracellular complexes that mediate host defense against pathogenic microorganisms by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) sense components of the type III secretion system (T3SS) and flagellar apparatus. Upon sensing of bacterial components, NAIPs recruit the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4). The resulting NAIP/NLRC4 inflammasome then recruits and activates caspase-1. Active caspase-1 mediates processing and secretion of IL-1 family cytokines and a proinflammatory cell death termed pyroptosis. In mice, bacterial ligands for four of seven distinct NAIPs are known: NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and both NAIP5 and NAIP6 recognize flagellin. In contrast, humans encode a single functional NAIP, raising the question of whether human NAIP senses one or multiple bacterial ligands. In this dissertation we show that, in contrast to murine NAIPs, promiscuous recognition of multiple bacterial ligands is conferred by a single human NAIP. We found that NAIP, but not NLRC4, appears to dictate the specificity or promiscuity of bacterial ligand recognition. In addition, our studies define a role for human NAIP in the inflammasome response to Salmonella Typhimurium infection. Overall, we provide a basis for understanding the mechanisms underlying human-specific innate immune responses against gram-negative bacterial infections. |
| 일반주제명 | Microbiology. Immunology. Cellular biology. Medicine. Health sciences. Pathology. |
| 언어 | 영어 |
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: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
