Host response processes and host-parasite interactions in <i>Trypanosoma brucei</i> infections

African trypanosomes are unicellular protozoan parasites that infect humans, livestock and wild animals. In Africa, trypanosomiasis has historically affected agricultural production and animal husbandry, having a high economic and social impact. The use of multi-omics technologies can help us to better understand host molecular response processes and the relative contribution of host susceptibility and pathogen virulence to disease severity. To this aim two genetically distinct strains of Trypanosoma brucei were inoculated into susceptible BALB/c mice and tolerant C57BL/6 mice, and samples from the spleen and plasma were collected from batches of mice at several time points after infection. RNA-seq and LC-MS were used to assess the fold-change gene expression and metabolite levels with respect to an uninfected control group. To integrate and interpret this complex data set we developed a novel method to reconstruct modules of co-expressed genes, which allows tracking of the conservation and divergence of modules across the different host-parasite specific sub-datasets. Strong correlations between transcriptome and metabolome were observed that revealed significant host-parasite genotype combination-specific changes in the expression of various metabolic pathways and immune response modules. This included pathways that are known to have an impact on immune cell function, such as glycolysis and the TCA cycle, but also pathways where the link is presently less well understood, such as purine metabolism. Intriguingly, correlations between genes and metabolites were often strongest in infections with the most severe pathogenesis, and in the opposite direction to those in less severe infections. In summary, our results provide novel insights in the link between metabolism and immune response, and have the potential to further our understanding of how the pathogen causes disease in the mammalian host.