Innate immune sensing of Plasmodium falciparum sporozoites and blood stages by human monocytes

Plasmodium sporozoites are potent inducers of adaptive immunity, but the underlying mechanisms of sporozoite sensing by innate cells are still unclear. To gain insights into the activation of human innate immune cells by sporozoites as opposed to activation by blood stages, we co-cultured GFP expressing P. falciparum sporozoites (PfSPZ) and blood stage parasites (PfRBC) with human monocytes. Comparing between the responses induced by PfSPZ and PfRBC revealed mostly genes with higher expression in PfSPZ-stimulated monocytes, most prominently COX-2 encoding PTGS2 and the chemokines CCL20 and CCL5. In addition, monocytes stimulated with PfSPZ displayed stronger plasma membrane injury than monocytes stimulated with PfRBC NF54-HGL P. falciparum sporozoites, expressing a GFP-luciferase fusion protein under the control of the CSP promotor, were isolated from A. stephensi salivary glands, sort-purified by flow cytometry and co-cultured with primary human T and B cell depleted PBMCs at an MOI of 0.5. Additionally, we co-cultured T and B cell depleted PBMCs from the same donors with magnetically enriched P. falciparum infected erythrocytes and control uninfected erythrocytes (RBC) at an MOI of 5 *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************