In previous studies we were able to explicitly trace the ontogeny and differentiation path of dendritic cells (DC) in the bone marrow, demonstrating clear differences in the development of conventional DC (cDC) and plasmacytoid DC (pDC). We showed that pDC develop via lymphoid progenitors, paralleling early B cell progenitors rather than cDC lineage development. Further, we identified progenitors specific to the cDC1, cDC2 and cDC3 lineages and were able to map these across tissues. However, most of these works were done under steady state conditions. Functional specialization or subset and tissue specific characteristics of each of these populations, DC or pDC, may only become obvious during inflammation. Thus, we now want to understand how functional specialization of DC subsets is achieved and altered between steady state versus inflammation, caused by viral infection.

Here, employing mouse models of viral infection with Influenza virus and murine cytomegalovirus, we characterize how tissue specific functions of pDC and cDC subsets are shaped and how their local progenitor pool versus bone marrow progenitor pool is altered – on a transcriptional and functional level. To address this, we combine in vitro and in vivo techniques with spectral flow cytometry, single-cell RNA sequencing and machine learning approaches. Our data indicate that indeed, both local (lung-specific) as well as systemic viral infection directly impacts functional differentiation of late-stage tissue “resident” and early bone marrow progenitor populations, as well as tissue-specific pDC and cDC subsets, resulting in frequency and phenotypical changes. We are currently investigating how these translate to functionality changes/specialization of each progenitor and DC population.