Comprehensive Transcriptome Meta-analysis to Characterize Host Immune Responses in Helminth Infections

Helminth infections affect more than a third of the world’s population. Despite very broad phylogenetic differences among helminth parasite species, a systemic Th2 host immune response is typically associated with long-term helminth infections, also known as the “helminth effect”. Many investigations have been carried out to study host gene expression profiles during helminth infections. The objective of this study is to determine if there is a common transcriptomic signature characteristic of the helminth effect across multiple helminth species and tissue types. To this end, we performed a comprehensive meta-analysis of publicly available gene expression datasets. After data processing and adjusting for study-specific effects, we identified ~700 differentially expressed genes that are changed consistently during helminth infections. Functional enrichment analyses indicate that upregulated genes are predominantly involved in various immune functions, including immunomodulation, immune signaling, inflammation, pathogen recognition and antigen presentation. Down-regulated genes are mainly involved in metabolic process, with only a few of them are involved in immune regulation. This common immune gene signature confirms previous observations and indicates that the helminth effect is robust across different parasite species as well as host tissue types. To the best of our knowledge, this study is the first comprehensive meta-analysis of host transcriptome profiles during helminth infections.Author Summary: Many studies have been conducted to understand the immune modulatory effects in helminth infections. To determine whether there is a common transcriptomic signature characteristic of the helminth effect, we performed a comprehensive meta-analysis of publicly available gene expression datasets. The results revealed a distinct pattern of gene expression that is consistent across multiple helminth species and host tissue types, with upregulated genes dominated by those involved in immune regulation, Th2 immunity and inflammatory responses.