Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34+ haematopoietic stem cells. These “humanized” mice are useful models to study human immunology and human-tropic infections, autoimmunity and cancer. Some human immune cell subsets are unable to fully develop or acquire full functional capacity due to lack of crossreactivity of many growth factors and cytokines between species. Conventional dendritic cells (cDC) in mice are categorized into cDC1, which mediate Th1 and CD8+ T-cell responses, and cDC2, mediating Th2 and Th17 responses. The likely human equivalents are CD141+ DC and CD1c+ DC subsets for mouse cDC1 and cDC2 respectively, but the extent of any interspecies differences is poorly characterized. Here we exploit the fact that human CD141+ DC and CD1c+ DC develop in humanized mice, to further explore their equivalency in vivo. Global transcriptome analysis of CD141+ DC and CD1c+ DC isolated from humanized mice demonstrated that they closely resemble those in human blood. Activation of DC subsets in vivo, with the TLR3 ligand polyI:C, and the TLR7/8 ligand R848 revealed that a core panel of genes consistent with DC maturation status were upregulated by both subsets. R848 specifically upregulated genes associated with Th17 responses by CD1c+ DC, whilst polyI:C upregulated IFN‐λ genes specifically by CD141+ DC. MYCL expression, known to be essential for CD8 + T-cell priming by mouse DC, was specifically induced in CD141+ DC after activation. Concomitantly, CD141+ DC were superior to CD1c+ DC in their ability to prime naïve antigen-specific CD8+ T-cells. Thus CD141+ DC and CD1c+ DC share a similar activation profiles in vivo but also have induce unique signatures that support specialized roles in CD8+ T cell priming and Th17 responses respectively. These data demonstrate humanized mice provide an attractive and tractable model to study human DC in vitro and in vivo.