The scope of this thesis is the immunomodulation by macrophages by metabolites and mRNA analogues used in vaccines. Human blood monocyte-derived macrophages are used as a model to study immune function. The work of this thesis shows how both the pro- and anti-inflammatory functions of macrophages are affected by different compounds with potential therapeutic applications. In chapter 2, we characterise the responses of macrophages to a new mRNA nucleotide analogue: 5-ethynyl uridine. This is particularly interesting because the mRNA is equipped with a chemical group from click-chemistry. The Nobel prize for click-chemistry was awarded this year to (among others) Carolyn Bertozzi. This technique will aid the development of mRNA vaccines by adding modality to mRNA therapies. The rest of the thesis focuses on the interaction of these immune cells with surrounding metabolites for potential therapeutic development. For instance, we found that the metabolite itaconate can contribute to a wound-healing phenotype, which could be interesting for wound treatment.