Status: Funded - Closed
Effect of helminth infection on Tuberculosis-specific immunology and DNA methylation
Andrew DiNardo, M.D.
BACKGROUND: Adults studies have shown that individuals who progress to TB disease are 1) more likely to be helminth infected and 2) to have more severe TB disease. In adults, helminth infections have been shown to polarize the immune system towards a Th2 (IL-4, IL-5 and IL-13) and Treg (CD25+Foxp3+IL-10+) CD4 lymphocyte
GAP: This study will be the first to evaluate 1) the attributable risk of helminth infection on TB disease and infection in a pediatric population, 2) how helminth infection modulates the TB-specific immune response, 3) the relationship of the TB-specific Th1 polyfunctional immune response to Th2 and Treg immunity at a single cell level, 4) the duration of helminth immune polarization and 5) the relationship between helminth-induced immune polarization with gene expression via DNA methylation.
HYPOTHESIS: Compared with helminth-uninfected children, those with helminth infection or in utero helminth exposure will have altered lymphocyte tuberculosis-specific immune phenotypes that correspond with epigenetic histone and DNA methylation marks.
METHODS: Lymphocytes from a well described longitudinal cohort will undergo flow cytometry based multi-parameter immune phenotyping and epigenetic studies (histone and DNA methylation analysis).
IMPACT: Understanding how and the duration of immune polarization by helminths will impact future vaccine studies as well as public health deworming policies and tuberculosis treatment guidelines.