Elucidating the differences in the innate immune sensing of Plasmodium berghei sporozoite and blood stages by mouse bone marrow-derived macrophages

Plasmodium sporozoites are potent inducers of adaptive immunity, but the underlying mechanisms of sporozoite sensing by innate cells have not been unraveled. To gain insights into how innate cells are activated by Plasmodium sporozoites, we co-cultured GFP expressing P. berghei sporozoites and blood stage parasites with BMDMs for 4 h and sorted GFP+ and GFP- BMDMs using FACS. GFP+ and GFP- BMDMs were then either prepared for RNA seq following the SmartSeq2 protocol, or re-cultured for 20 h in absence of additional stimuli before processing for RNA sequencing. From these experiments, we learned that sporozoites induce a distinct activation signature in BMDMs that is different from that induced by blood stage parasites or LPS. Pathway analysis revealed a 'response to wounding' phenotype present at both timepoints. Taken together, this data reveals a unique innate activation profile induced by sporozoites that could help pinpoint the cause of the strong ability of sporozoites to induce adaptive immune responses.