Infectious Sporozoites of Plasmodium berghei Effectively Activate Liver CD8α⁺ Dendritic Cells

Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete sterile protection against Plasmodia liver-stage (LS) infection that lasts about 6 to 9 months in mice. We have found that the intermittent infectious sporozoite challenge to immune mice following RAS vaccination extends the longevity of sterile protection by maintaining CD8⁺ T cell memory responses to LS infection. It is reported that CD8α⁺ dendritic cells (DCs) are involved in the induction of LS-specific CD8⁺ T cells following RAS or genetically attenuated parasite (GAP) vaccination. In this study, we demonstrate that CD8α⁺ DCs respond differently to infectious sporozoite or RAS inoculation. The higher accumulation and activation of CD8α⁺ DCs was seen in the liver in response to infectious sporozoite 72 h postinoculation and found to be associated with higher expression of chemokines (CCL-20 and CCL-21) and type I interferon response via toll-like receptor signaling in liver. Moreover, the infectious sporozoites were found to induce qualitative changes in terms of the increased MHCII expression as well as costimulatory molecules including CD40 on the CD8α⁺ DCs compared to RAS inoculation. We have also found that infectious sporozoite challenge increased CD40L-expressing CD4⁺ T cells, which could help CD8⁺ T cells in the liver through "licensing" of the antigen-presenting cells. Our results suggest that infectious sporozoite challenge to prior RAS immunized mice modulates the CD8α⁺ DCs, which might be shaping the fate of memory CD8⁺ T cells against Plasmodium LS infection.