Dectin-IL-17 axis, candidemia, and aging

描述（由申请人提供）：老年人更容易受到严重感染，年龄是念珠菌血流感染死亡率的单一最强预测因子。Th17 T细胞是最近被描述的一种重要的效应T细胞亚群，它产生IL-17，并与抗真菌和抗分枝杆菌免疫以及几种自身免疫疾病有关。抗原呈递细胞上通过Dectin通路的信号传导促进特异性T细胞向Th17功能表型的分化。我们的初步数据以及动物数据表明，Th17 T细胞在人类衰老过程中失调，这使我们提出了一种假设，即人类衰老与Dectin-IL-17轴的变化有关，导致老年人念珠菌病的次佳免疫反应和不良结果。这一假设将通过研究人类年龄相关的Dectin -Th17轴的变化来验证，并确定Dectin的表达或功能是否减少并导致老年人Th17反应失调。此外，我们将广泛描述来自老年人的Th17 T细胞的诱导表型。我们预计这些研究将导致对老年人免疫反应调节的更好理解，并可能有助于识别念珠菌感染后不良后果风险增加的老年人。

DESCRIPTION (provided by applicant): Older adults are more susceptible to severe infections and age is the single strongest predictor of mortality in Candida blood stream infections. Th17 T cells are a recently described important subset of effector T cells that produce IL-17 and have been implicated in antifungal and anti-mycobacterial immunity, as well as several auto-immune disorders. Signaling through the Dectin pathway on antigen-presenting cells promotes differentiation of specific T cells to the Th17 functional phenotype. Our preliminary data, as well as animal data suggest a dysregulation of Th17 T cells in human aging leading us to propose the hypothesis that human aging is associated with changes in the Dectin-IL-17 axis resulting in suboptimal immune responses and adverse outcomes in candidemia in older adults. This hypothesis will be tested by studying human age-related changes in the dectin-Th17 axis and determining whether Dectin expression or function is decreased and contributes to dysregulation of Th17 responses in older adults. In addition, we will extensively describe the induction of phenotype of Th17 T cells derived from older adults. We anticipate that these studies will lead to an improved understanding of regulation of immune responses in older adults, and may help to identify older adults at increased risk for adverse outcomes after candidemia.