Grant: Travel Awards - Institute Community Support

Humans can get exposed to pathogens in different ways, leading to air, food/water, blood, vector-borne or sexually transmitted infections. Independently of how pathogens are transmitted, they are often capable of resisting the initial host-immune response and spread to other organs through a process called dissemination. Pathogen dissemination is described in diseases such as AIDS, Malaria, Lyme disease and Covid-19, playing a major role in global health. Another example is Leishmaniasis, a vector-borne disease transmitted through the bite of an infected sandfly that deposits a protozoan parasite, Leishmania, into the skin of a host. Depending on the parasite specie, the parasite can disseminate out of the skin reaching visceral organs and causing fatal disease. Despite the relevance of the dissemination process the mechanisms by which this happens are largely unknown. In this work we established a model of disseminated infection performing a "skin prick" inoculation, performed by pricking the skin under a drop of concentrated Leishmania parasites. We infected mice with a strain of Leishmania that disseminates in people and tracked parasite dissemination towards the draining lymph node (dLN), spleen and liver over time. Skin prick inoculation deposited physiological low doses of parasites into the dermis, mimics the prototypical robust initial neutrophil infiltrate observed after vector transmission, and resulted in parasite dissemination. Surprisingly, we found rapid extracellular parasite dissemination to the dLN. The depletion of neutrophils; absence of monocyte recruitment and blocking dendritic cell migration did not impair this early dissemination, suggesting it occurs in an extra-cellular manner. In conclusion, our skin prick method recapitulates important aspects of natural Leishmania transmission. Importantly, our data indicates that a host phagocytic cell is not required for early dissemination to the dLN.