Role of Th17 in Severe and Recurrent C. difficile Infection

Th17 在严重和复发性艰难梭菌感染中的作用

基本信息

  • 批准号:
    10443698
  • 负责人:
  • 金额:
    $ 78.41万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-24 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

Project Summary Introduction: We propose to Identify the mechanisms by which an intestinal Th17 immune response contributes to severe and recurrent Clostridioides difficile infection (CDI) and explore the immune mechanism by which fecal microbiota transplant (FMT) protects. Hypothesis: Th17 cells contribute to severe CDI and to recurrence. Premise: Failure of antibiotic treatment of CDI (i.e. death or recurrence) is due to a gut Th17 immune response. Significance: C. difficile is the leading cause of hospital-acquired infection in the United States. One in five patients with CDI fails antibiotic treatment and as a result suffers a recurrent infection or death. This proposal will explore if immunotherapy would improve treatment of CDI, specifically by testing the importance of gut Th17 immune responses in CDI severity and recurrence Investigators: Dr. William Petri at the University of Virginia has discovered that Type-17 immunity causes more severe disease during CDI. This has included showing that IL-23 knockout mice have increased survival, reduced neutrophil influx, and reduced tissue pathology (Buonomo et al 2013), that the Th17 polarizing cytokines IL-6 and IL-23 are associated with more severe disease in humans, that type 2 immunity protects by countering Th17 (Frisbee et al 2019), and that adoptive transfer of Th17 cells is sufficient to enhance CDI mortality (Saleh et al 2019). He is joined by Dr. Ann Hays who directs the complicated C. difficile clinic at UVA and the biostatistical expertise of Dr. Jennie Ma. Innovation: The proposed research by testing if Th17 cells have a role in severe CDI as well as recurrent CDI will be paradigm shifting, as this is a field of research that in the past has focused on targeting the bacterium or the microbiota for therapy. This proposal will instead test if the induction of a Th17 immune response in addition to the bacterium and microbiota are causing disease. Approach: Specific Aim 1: SEVERE CDI - Identify the mechanisms by which a Th17 immune response leads to severe C. difficile infection (CDI) Specific Aim 2: RECURRENT CDI - Test the role of Th17 cells and the Th17-recruiting chemokine CCL5 in recurrent CDI Specific Aim 3: FMT – Determine if FMT protects from primary and recurrent CDI by inducing IL-33 that blocks the action of Th17. Environment: Key to success are the complementary expertise of the Petri lab in the mucosal immunology of enteric infections, and the clinical expertise in FMT for complicated C. difficile infection of Dr. Ann Hays.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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William A Petri其他文献

Environmental enteropathy and malnutrition: do we know enough to intervene?
  • DOI:
    10.1186/s12916-014-0187-1
  • 发表时间:
    2014-10-14
  • 期刊:
  • 影响因子:
    8.300
  • 作者:
    William A Petri;Caitlin Naylor;Rashidul Haque
  • 通讯作者:
    Rashidul Haque
The Environmental Enteric Dysfunction Biopsy Initiative (EEDBI) Consortium: mucosal investigations of environmental enteric dysfunction
环境肠道功能障碍活检倡议(EEDBI)联盟:环境肠道功能障碍的黏膜研究
  • DOI:
    10.1016/j.ajcnut.2024.02.003
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Donna M Denno;Sheraz Ahmed;Tahmeed Ahmed;S Asad Ali;Beatrice Amadi;Paul Kelly;Sarah Lawrence;Mustafa Mahfuz;Chelsea Marie;Sean R Moore;James P Nataro;William A Petri;Peter B Sullivan;Phillip I Tarr;Kumail Ahmed;Md Ashraful Alam;Barrett H Barnes;SM Khodeza Nahar Begum;Stephen M Borowitz;Kanta Chandwe;Fayaz Umrani
  • 通讯作者:
    Fayaz Umrani
Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children
孟加拉国、巴基斯坦和赞比亚营养不良儿童队列研究与美国儿童相比的环境性肠功能障碍的组织病理学基础
  • DOI:
    10.1016/j.ajcnut.2024.02.028
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Paul Kelly;Kelley VanBuskirk;David Coomes;Samer Mouksassi;Gerald Smith;Zehra Jamil;Md Shabab Hossain;Sana Syed;Chelsea Marie;Phillip I Tarr;Peter B Sullivan;William A Petri;Donna M Denno;Tahmeed Ahmed;Mustafa Mahfuz;S Asad Ali;Sean R Moore;I Malick Ndao;Guillermo J Tearney;Ömer H Yilmaz;Kanekwa Zyambo
  • 通讯作者:
    Kanekwa Zyambo
Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction
环境性肠功能障碍中小肠炎症和上皮参数的多重免疫组化评估
  • DOI:
    10.1016/j.ajcnut.2024.02.033
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Kelley VanBuskirk;Monica Mweetwa;Tad Kolterman;Shyam Raghavan;Tahmeed Ahmed;S Asad Ali;SM Khodeza Nahar Begum;Ellen Besa;Donna M Denno;Zehra Jamil;Paul Kelly;Mustafa Mahfuz;Sean R Moore;Samer Mouksassi;William A Petri;Phillip I Tarr;Peter B Sullivan;Christopher A Moskaluk;Kumail Ahmed;Sheraz Ahmed;Omer H Yilmaz
  • 通讯作者:
    Omer H Yilmaz
Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers
十二指肠转录组学显示了全球多个中心环境肠道功能障碍儿童组织炎症和免疫细胞浸润的特征
  • DOI:
    10.1016/j.ajcnut.2024.02.023
  • 发表时间:
    2024-09-01
  • 期刊:
  • 影响因子:
    6.900
  • 作者:
    Chelsea Marie;Subhasish Das;David Coomes;Tahmeed Ahmed;S Asad Ali;Junaid Iqbal;Paul Kelly;Mustafa Mahfuz;Sean R Moore;William A Petri;Phillip I Tarr;Lee A Denson;Kumail Ahmed;Sheraz Ahmed;Md Ashraful Alam;David Auble;SM Khodeza Nahar Begum;Ellen Besa;Mubanga Chama;Donna M Denno;Kanekwa Zyambo
  • 通讯作者:
    Kanekwa Zyambo

William A Petri的其他文献

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{{ truncateString('William A Petri', 18)}}的其他基金

Role of Th17 in Severe and Recurrent C. difficile Infection
Th17 在严重和复发性艰难梭菌感染中的作用
  • 批准号:
    10223165
  • 财政年份:
    2020
  • 资助金额:
    $ 78.41万
  • 项目类别:
Role of Th17 in Severe and Recurrent C. difficile Infection
Th17 在严重和复发性艰难梭菌感染中的作用
  • 批准号:
    10653065
  • 财政年份:
    2020
  • 资助金额:
    $ 78.41万
  • 项目类别:
Subunit Vaccine for Cryptosporidiosis
隐孢子虫病亚单位疫苗
  • 批准号:
    10312809
  • 财政年份:
    2020
  • 资助金额:
    $ 78.41万
  • 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
  • 批准号:
    10176548
  • 财政年份:
    2018
  • 资助金额:
    $ 78.41万
  • 项目类别:
NICHD Global Network for Women’s and Children’s Health Research: Research Units
NICHD 全球妇女和儿童健康研究网络:研究单位
  • 批准号:
    10746195
  • 财政年份:
    2018
  • 资助金额:
    $ 78.41万
  • 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
  • 批准号:
    9754231
  • 财政年份:
    2018
  • 资助金额:
    $ 78.41万
  • 项目类别:
University of Virginia - icddr,b Research Unit for Women's and Children's Health Research
弗吉尼亚大学 - icddr,b 妇女和儿童健康研究单位
  • 批准号:
    10413887
  • 财政年份:
    2018
  • 资助金额:
    $ 78.41万
  • 项目类别:
Role of Type 2 Immunity in Innate Protection from C. difficile
2 型免疫在艰难梭菌先天保护中的作用
  • 批准号:
    10467414
  • 财政年份:
    2016
  • 资助金额:
    $ 78.41万
  • 项目类别:
Role of Type 2 Immunity in Innate Protection from C. difficile
2 型免疫在艰难梭菌先天保护中的作用
  • 批准号:
    10561651
  • 财政年份:
    2016
  • 资助金额:
    $ 78.41万
  • 项目类别:
Role of IL-23 in the Immunopathogenesis of C. difficile colitis
IL-23 在艰难梭菌结肠炎免疫发病机制中的作用
  • 批准号:
    9057951
  • 财政年份:
    2015
  • 资助金额:
    $ 78.41万
  • 项目类别:

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SBIR II 期:开发尿液试纸测试,可以指导复杂尿路感染的立即和适当的抗生素治疗
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