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Salmonella-specific Th1 cell function and residence

沙门氏菌特异性 Th1 细胞功能和驻留

基本信息

批准号：
10543144
负责人：
STEPHEN J MCSORLEY
金额：
$ 38.29万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-10 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543144
关键词：
Activities of Daily Living Africa Antigen Targeting Antigens Area Attenuated Vaccines Bacteremia Bacteria Biology Bone Marrow CD4 Positive T Lymphocytes Cell physiology Cells Cellular biology Cessation of life Characteristics Childhood Clinical Trials Data Developing Countries Development Disease Effectiveness Epitopes Exposure to Failure Foundations Generations Genetic Goals Human IL18 gene Immunity Immunization Immunize Infant Infection Interferon Type II Knowledge Laboratories Licensing Life Liver Lymphocyte MHC Class II Genes Memory Mus Persons Phagocytes Predisposition Reagent Recurrent disease Reporting Role Salmonella Salmonella Vaccines Salmonella infections Signal Transduction Solid Subunit Vaccines Systemic disease T cell response Testing Th1 Cells Tissues Typhoid Fever Typhoid Vaccine Vaccination Vaccine Antigen Vaccines Virulent Visualization combat contaminated water impaired capacity improved memory CD4 T lymphocyte mouse model novel vaccines pathogen persistent bacteria residence response vaccination strategy vaccine development

项目摘要

Typhoid and Non-Typhoidal Salmonellosis (NTS) are systemic diseases that annually cause 1 million global deaths. Greater understanding of protective immunity to Salmonella will be required if safe and effective vaccines for these diseases are to become a reality. Our application examines the fundamental biology of protective CD4 Th1 cells elicited by live vaccines that provide robust protective immunity. Our experimental approach is unique in that it utilizes natural water contamination challenge, uses a mouse model where CD4 Th1 cells participate actively in bacterial clearance, and allows for direct visualization of endogenous Salmonella-specific CD4 T cells, using reagents recently developed by our laboratory. Our application specifically proposes to, (i) examine the role of non-cognate Th1 cell stimulation in Salmonella clearance, (ii) determine the role of tissue-resident memory cells in the elimination of persistent bacteria, and (iii) examine whether these two functional aspects of Th1 cell memory can be induced by a sub-unit immunization strategy. Understanding these issues will increase our knowledge of Salmonella-specific CD4 Th1 cell biology and could be vital for the development of safe and effective vaccines for typhoid and NTS.

伤寒和非伤寒沙门氏菌病（NTS）是每年导致全球100万人死亡的全身性疾病。死亡如果沙门氏菌是安全有效的，这些疾病的疫苗将成为现实。我们的应用程序研究了活疫苗引发的保护性CD 4 Th 1细胞可提供强大的保护性免疫力。我们的实验这种方法的独特之处在于它利用了天然水污染的挑战，使用了一种小鼠模型，其中CD4 Th1细胞积极参与细菌清除，并允许直接观察内源性沙门氏菌特异性CD4 T细胞，使用我们实验室最近开发的试剂。我们的应用程序特别提出，（i）检查非同源Th1细胞刺激在沙门氏菌清除中的作用，（ii）确定组织驻留记忆细胞在消除持久性细菌中的作用，以及（iii）检查 Th 1细胞记忆的这两个功能方面是否可以通过亚单位免疫策略诱导。了解这些问题将增加我们对沙门氏菌特异性CD4 Th1细胞生物学的了解，这对开发安全有效的伤寒和NTS疫苗至关重要。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice.

Th1细胞可用于从小鼠的雌性生殖道的主要清除衣原体的主要清除。

DOI：
10.1371/journal.ppat.1010333
发表时间：
2022-03
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Rixon JA;Depew CE;McSorley SJ
通讯作者：
McSorley SJ

CD4+ T cell immunity to Salmonella is transient in the circulation.

DOI：
10.1371/journal.ppat.1010004
发表时间：
2021-10
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Peres NG;Wang N;Whitney P;Engel S;Shreenivas MM;Comerford I;Hocking DM;Erazo AB;Förster I;Kupz A;Gebhardt T;McColl SR;McSorley SJ;Bedoui S;Strugnell RA
通讯作者：
Strugnell RA

Optimal generation of hepatic tissue-resident memory CD4 T cells requires IL-1 and IL-2.

DOI：
10.1073/pnas.2214699120
发表时间：
2023-04-18
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Depew, Claire E.;Rixon, Jordan A.;McSorley, Stephen J.
通讯作者：
McSorley, Stephen J.

Cutting Edge: Optimal Formation of Hepatic Tissue-Resident Memory CD4 T Cells Requires T-bet Regulation of CD18.

前沿技术：肝组织驻留记忆 CD4 T 细胞的最佳形成需要 CD18 的 T-bet 调节。

DOI：
10.4049/jimmunol.2300017
发表时间：
2023
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
0
作者：
Depew,ClaireE;Nguyen,AlanaT;Franke,MarissaC;Calderon,Jesica;Sciammas,Roger;McSorley,StephenJ
通讯作者：
McSorley,StephenJ

Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells.