Salmonella-specific Th1 cell function and residence

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 由活疫苗引发的保护性CD4 Th1细胞，提供强大的保护性免疫。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 Th1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。

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.