東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Sulfated DAMPS Mobilize Human GBPs f...

Bradfield, Clinton James.

FindBook

Google Book

Amazon

博客來

Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens./
作者:	Bradfield, Clinton James.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
面頁冊數:	278 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
Contained By:	Dissertation Abstracts International77-12B(E).
標題:	Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10151738
ISBN:	9781369064421

Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens.
Bradfield, Clinton James.

Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 278 p.

Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.

Thesis (Ph.D.)--Yale University, 2016.

Microbial infections embody a strong evolutionary pressure to which higher organisms must respond. Due to the evolutionary advantage microbes maintain over higher organisms, pathogens have established a variety of ways to co-opt beneficial cellular pathways as well as to resist, avoid, and inactivate hazardous evolutionarily-conserved cellular defenses [1]. Higher organisms similarly respond through adaptation and species divergence to restrain hazardous, and maintain beneficial, trans-phyla interactions. Although the co-evolutionary dialogues between hosts and microbes are complex, the ability of higher organisms to recognize and mount appropriate, effective responses is obligatory to maintain biological fitness.

ISBN: 9781369064421Subjects--Topical Terms:

611031
Immunology.

Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens.
LDR:05071nmm a2200349 4500 001 2123976
005 20171023101702.5
008 180830s2016 ||||||||||||||||| ||eng d
020 $a 9781369064421
035 $a (MiAaPQ)AAI10151738
035 $a AAI10151738
040 $a MiAaPQ $c MiAaPQ
100 1 $a Bradfield, Clinton James. $3 3285933
245 1 0 $a Sulfated DAMPS Mobilize Human GBPs for Cell-autonomous Immunity Against Bacterial Pathogens.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 278 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-12(E), Section: B.
500 $a Adviser: John David MacMicking.
502 $a Thesis (Ph.D.)--Yale University, 2016.
520 $a Microbial infections embody a strong evolutionary pressure to which higher organisms must respond. Due to the evolutionary advantage microbes maintain over higher organisms, pathogens have established a variety of ways to co-opt beneficial cellular pathways as well as to resist, avoid, and inactivate hazardous evolutionarily-conserved cellular defenses [1]. Higher organisms similarly respond through adaptation and species divergence to restrain hazardous, and maintain beneficial, trans-phyla interactions. Although the co-evolutionary dialogues between hosts and microbes are complex, the ability of higher organisms to recognize and mount appropriate, effective responses is obligatory to maintain biological fitness.
520 $a Host-microbe interactions first occur at the level of the innate immune system where basal cellular processes set up restrictive barriers to control microbial replication and regulate microbial behavior. Once these barriers are breached, sensory proteins alter dynamic cell behaviors to more effectively restrict infectious organisms. Here, homeostatic perturbations such as the presence of microbial ligands (PAMPs) or alterations in the canonical cellular environment (DAMPs) trigger cellular cascades to enlist intracellular defenses and alert neighboring cells [2-4].
520 $a Interestingly, vertebrates maintain diverse, dynamic cellular environments. Herein cytokine stimulation reprograms cells to enact specific functions. Interferon gamma (IFN-gamma) is a potent immunologic cytokine that utilizes JAK-STAT signaling to up-regulate hundreds to thousands of gene products in all nucleated cells. This broad, cellular reprograming facilitates control a diverse range of infectious agents [5, 6] Although much of the research on IFN-gamma focuses on understanding enhancement of the bio-synthetic and bio-destructive potential of classical immune cells, fewer studies concentrate on understanding IFN-gamma mediated bio-restriction of bacteria in non-myeloid lineages, cells that are primary sites of infection [7-9].
520 $a IFN-gamma is essential for cellular immunity where induced gene products are capable of restricting intracellular pathogens; however, mechanistic understanding of these processes remains largely enigmatic. Recently, our lab has elucidated immune-related roles for a family of p65 Guanylate Binding Proteins (GBPs) in mice through enhanced assembly of immune complexes such as the inflammasome and the NADPH Oxidase (NOX2) machineries [10, 11]. We then questioned whether this multi-gene family could aid in IFN-gamma mediated restriction of intracellular bacteria that infect epithelia lacking traditional immune-effector machines employed by macrophages.
520 $a In this study we demonstrate that IFN-gamma effectively reprograms human epithelial cells to augment cell-autonomous immune defenses against intracellular Salmonella typhimurium and Listeria monocytogenes through hierarchical employment of IFN-gamma inducible p65 GTPases GBP1 and GBP2. We find that these dynamin-family GTPases require GTPase, oligomerization, and prenylation motifs to redistribute from the cytosol to damaged pathogen-containing vacuoles where they aid in restriction of bacteria. Surprisingly, we find that GBPs mobilization occurs in response to cytosolic exposure of a newly discovered danger-associated molecular pattern normally "hidden" from the host cytosol. Here GBP1 specifically binds sulfated glycosphingolipids to attain juxta-bacterial positioning necessary for bacterial restriction. This mobilization and subsequent bacterial restriction is distinct from reported lectin and autophagic bacterial restriction pathways. Remarkably, depletion of cellular sulfates completely abrogates both IFN-gamma induced bacterial restriction and GBP mobilization which could be partially restored by in-trans administration of sulfated glycosphingolipids. Collectively, these data establish that IFN-gamma augments cell-autonomous immunity in epithelial cells by coupling immune effector machineries to sulfated host DAMPs through GBP1 and GBP2.
590 $a School code: 0265.
650 4 $a Immunology. $3 611031
650 4 $a Cellular biology. $3 3172791
650 4 $a Microbiology. $3 536250
690 $a 0982
690 $a 0379
690 $a 0410
710 2 $a Yale University. $3 515640
773 0 $t Dissertation Abstracts International $g 77-12B(E).
790 $a 0265
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10151738