Schistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes.

Area of Science:

• Immunology
• Epigenetics
• Infectious Disease

Background:

• Epigenetic modifications, including DNA methylation, are crucial for regulating immune cell function and phenotype.
• Helminth coinfections can significantly impact host immune responses, potentially influencing susceptibility to other infections like tuberculosis (TB).

Purpose of the Study:

• To investigate the longitudinal epigenetic alterations in CD4+ T cells caused by ascariasis and schistosomiasis.
• To determine the downstream effects of these epigenetic changes on TB-specific and BCG-induced immune responses.

Main Methods:

• Analysis of DNA methylation patterns in CD4+ T cells from a longitudinal cohort of TB-exposed children with and without helminth infections.
• Utilized targeted real-time quantitative PCR and Ag-specific multidimensional flow cytometry to assess gene methylation and immune cell function.
• Evaluated gene ontology pathways related to immune signaling and cell proliferation.

Main Results:

• Helminth infections (ascariasis and schistosomiasis) were associated with 751 differentially methylated genes in CD4+ T cells, predominantly hypermethylation.
• Identified significant alterations in IFN-γ signaling, Th1 pathway, and cellular proliferation pathways.
• Observed decreased TB-specific IFN-γ and TNF production, and increased IL-4 production, indicating a shift in CD4+ T cell phenotype.
• These immune perturbations persisted for at least 6 months post-deworming in individuals with schistosomiasis.

Conclusions:

• Helminth infections induce persistent DNA methylation changes in CD4+ T cells, leading to immune dysregulation.
• These epigenetic alterations inhibit effective TB-specific immune control.
• The duration of these helminth-induced immune changes is specific to the type of helminth infection.