Dectin-IL-17 axis, candidemia, and aging

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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. PUBLIC HEALTH RELEVANCE: In this project, we will study how our immune system changes as we get older. We will focus on a specific group of cells of the immune system; Th17 T cells. These cells are known to play a role in the immune response to fungal infections. Therefore, we will also study patients in various age groups who have a serious fungal infection to see if age influences how these cells function during infection.