Do ApoptoticPlasmodium‐Infected Hepatocytes Initiate Protective Immune Responses?

To the Editor —In an article recently published in the Journal of Infectious Diseases Leiriao et al. [1] suggested that the uptake by dendritic cells (DCs) of antigens derived from apoptotic Plasmodium-infected hepatocytes is a key factor in the induction of sterile protective immunity by inoculation with irradiated sporozoites. This proposal was based on 2 experimental observations: that there is an increase in the occurrence of apoptotic host cells when they are infected with irradiated rather than normal sporozoites and that macrophages and DCs bearing parasite proteins are derived from apoptotic Plasmodium-infected hepatocytes in the livers of mice immunized with irradiated sporozoites. The authors implied that presentation by these cells would be responsible for the protection induced by irradiated sporozoites. The data prompted a supportive commentary by James [2], who had previously hypothesized that invasion by pathogens would induce apoptosis of host cells to limit the infection [3]. Given that costly vaccine development programs strive to reproduce and extend the reference standard of sterile protection obtained after immunization with irradiated sporozoites, the elucidation of the events that efficiently prime the immune response is highly desirable, and, thus, the conclusions of Leiriao et al. [1] merit careful scrutiny