Innate immune sensing of Plasmodium sporozoite cell traversal drives protective T cell responses.

Abstract

Attenuated Plasmodium sporozoites (SPZs) are being tested as a potential malaria vaccine as they elicit robust adaptive immune responses that protect against parasite challenge. Yet how they engage the innate immune system remains poorly understood. Here we isolated pure GFP+ Plasmodium berghei and Plasmodium falciparum SPZs, and sorted them onto mouse bone marrow-derived macrophages or human peripheral blood mononuclear cells to assess innate immune activation using bulk and single-cell RNA sequencing. SPZs induced a distinctive activation pattern in vitro resembling cell wounding responses, consistent with their ability to traverse host cells en route to the liver. Cell traversal-deficient..