Tissue-specific cellular immune responses to malaria pre-erythrocytic stages

Complete and long-lasting protective immunity against malaria can be achieved through vaccination with invasive live attenuated Plasmodium sporozoites, the motile stage inoculated in the host skin during a mosquito bite. Protective immunity relies primarily on effector CD8⁺ T cells targeting the parasite in the liver. Understanding the tissue-specific features of the immune response is emerging as a vital requirement for understanding protective immunity. The small parasite inoculum, the scarcity of infected cells and the tolerogenic properties of the liver represent hurdles for the establishment of protective immunity in endemic areas. In this review, we discuss recent advances on liver-specific features of immunity including innate recognition of malaria pre-erythrocytic stages, CD8⁺ T cell interactions with infected hepatocytes, antigen presentation for effective CD8⁺ T cell responses and generation of liver-resident memory CD8⁺ T cells. A better understanding of the factors involved in the induction and maintenance of effector CD8⁺ T cell immunity against malaria pre-erythrocytic stages is crucial for the development of an effective vaccine targeting the initial phase of malaria infection.