Dendritic cells (DCs) and monocytes are innate immune cells involved in recognising pathogens or damage-associated molecules, triggering adaptive immune responses, and maintaining homeostatic conditions. DCs and monocytes are collectively referred to as Mononuclear Phagocyte System (MPS) cells, and their origin and development in humans still need elucidating. Lineage-determining cytokine receptors (LDCRs) are growth factors with a pivotal role in haematopoietic cell differentiation and survival. These receptors are retained on mature cell surface, suggesting an active role after differentiation. Here, the link between DCs and monocytes at a developmental level was assessed at steady state using CSF1R, aLDCR previously known as expressed only on macrophages, but now proved to be on all cells of the MPS. The MPS was further studied across multiple diseases, to assess its development or effector state. DCs and monocytes were assessed in two distinct anti-malarial vaccine challenges. Both vaccines targeted the same blood-stage Plasmodium falciparum antigen apical membrane protein 1 (AMA1),involved in erythrocyte invasion by malaria. One vaccine formulation was based on a prime-boost viral delivery of the antigen, while the other vaccine consisted of the recombinant protein administered with a liposome-based adjuvant system. The MPS was greatly affected and reshaped, with cell fluctuations in percentages depending on the vaccine formulation. The viral-vectored vaccine also seemed to activate cells more effectively compared to the protein vaccine. LDCR and surface marker expression in CSF1R+ cells was also affected by the different vaccine vector components.