Integrated Gene Co-Expression Analysis of Host–Parasite Transcriptomes Reveals Mechanisms of Host Modulation

How parasites and hosts interact at the molecular level is one of the key questions in parasitology. However, due to the diverse consequences of parasite infection on host molecular physiology, it can be challenging to identify pathways that are directly targeted by parasites. This applies in particular to non-model systems such as the interaction between the parasitic tapeworm Anomotaenia brevis and its intermediate host, the ant Temnothorax nylanderi, whose phenotype is strongly altered by the infection. By integrating transcriptome information from hosts and their parasites in a combined weighted gene co-expression network analysis (WGCNA), we identified gene networks and candidate genes critical for this parasite-host interaction. Our analysis revealed tight statistical links between the expression of specific parasite genes and key host molecular pathways. The gene networks and correlations identified are consistent with those playing a major role in model parasite-host systems, a validation of our approach. Finally, we gained first insights into the functions of previously unannotated parasite genes, but which can be considered candidates for host manipulation. The expression of genes encoding proteins secreted by the parasite into the host was associated with host genes involved in oxidative stress resistance, metabolism, muscle function, immunity, and cuticular sclerotization, suggesting that the parasite may modulate these molecular pathways in the host. Our findings advance our understanding of parasite interference and highlight key mechanisms in the evolution of these complex molecular interactions.