Leishmania major drives host phagocyte death and cell-to-cell transfer depending on intracellular pathogen proliferation rate

• DOI: 10.1172/jci.insight.169020
• Publication Date: 2023-06-13T16:00:38Z
• Authors: Iris Baars; Moritz Jaedtka; Leon-Alexander De...; Yan Fu; Tobias Franz; Juliane Mohr; Patricia Gintschel; Hannes Berlin; Angelina Degen; Sandra Freier; Stefan Rygol; Burkhart Schraven; Sascha Kahlfuß; Ger van Zandbergen; Andreas J. Müller
• Keywords: Phagocyte; Intracellular parasite

The virulence of intracellular pathogens relies largely on the ability to survive and replicate within phagocytes, but also release transfer into new host cells. Such cell-to-cell could represent a target for counteracting microbial pathogenesis. However, our understanding underlying cellular molecular processes remains woefully insufficient. Using intravital 2-photon microscopy caspase-3 activation in Leishmania major (L. major)-infected live skin, we show increased apoptosis cells infected by parasite. Also, parasite occurred directly without detectable extracellular state, was associated with concomitant uptake material from original cell. These vivo findings were fully recapitulated infections isolated human phagocytes. Furthermore, observed that high pathogen proliferation cell death cells, long-term residency an only possible slowly proliferating parasites. Our results therefore suggest L. drives its own dissemination phagocytes inducing proliferation-dependent manner.