CD11c-expressing Ly6C+CCR2+ monocytes constitute a reservoir for efficient Leishmania proliferation and cell-to-cell transmission

The virulence of intracellular pathogens such as Leishmania major (L.major) relies largely on their ability to undergo cycles of replication within phagocytes, release, and uptake into new host cells.While all these steps are critical for successful establishment of infection, neither the cellular niche of efficient proliferation, nor the spread to new host cells have been characterized in vivo.Here, using a biosensor for measuring pathogen proliferation in the living tissue, we found that monocyte-derived Ly6C + CCR2 + phagocytes expressing CD11c constituted the main cell type harboring rapidly proliferating L. major in the ongoing infection.Synchronization of host cell recruitment and intravital 2-photon imaging showed that these high proliferating parasites preferentially underwent cell-to-cell spread.However, newly recruited host cells were infected irrespectively of their cell type or maturation state.We propose that among these cells, CD11c-expressing monocytes are most permissive for pathogen proliferation, and thus mainly fuel the cycle of intracellular proliferation and cell-to-cell transfer during the acute infection.Thus, besides the well-described function for priming and activating T cell effector functions against L. major, CD11c-expressing monocyte-derived cells provide a reservoir for rapidly proliferating parasites that disseminate at the site of infection. Author summaryInfection with Leishmania parasites can result in chronic disease of several months duration, often accompanied with disfiguring and disabling pathologies.Central to Leishmania virulence is the capability to survive and multiply within professional phagocytes.While it is assumed that the parasites at some point have to exit the infected cell and infect new cells, the cycle of intracellular multiplication, release, and uptake into new host cells has