RESEARCH ARTICLE Rapid Sequestration of Leishmania mexicana by Neutrophils Contributes to the Development of Chronic Lesion

The protozoan Leishmania mexicana parasite causes chronic non-healing cutaneous le-sions in humans and mice with poor parasite control. The mechanisms preventing the de-velopment of a protective immune response against this parasite are unclear. Here we provide data demonstrating that parasite sequestration by neutrophils is responsible for dis-ease progression in mice. Within hours of infection L.mexicana induced the local recruit-ment of neutrophils, which ingested parasites and formed extracellular traps without markedly impairing parasite survival. We further showed that the L.mexicana-induced re-cruitment of neutrophils impaired the early recruitment of dendritic cells at the site of infec-tion as observed by intravital 2-photon microscopy and flow cytometry analysis. Indeed, infection of neutropenic Genistamice and of mice depleted of neutrophils at the onset of in-fection demonstrated a prominent role for neutrophils in this process. Furthermore, an in-crease in monocyte-derived dendritic cells was also observed in draining lymph nodes of neutropenic mice, correlating with subsequent increased frequency of IFNγ-secreting T helper cells, and better parasite control leading ultimately to complete healing of the lesion