Malaria is caused by parasitic protozoans of the genus Plasmodium. Only their blood stages are responsible for morbidity and mortality, which develop and multiply within host red blood cells. The main effector organ against blood-stage malaria is the spleen, which is able to eliminate senescent and other aberrant erythrocytes including Plasmodium-parasitized erythrocytes. Additionally, the liver with its intrinsic immune system is increasingly recognized as an effector organ against blood-stage malaria, with the Kupffer cells with their erythrophagocytic capacity regarded as mainly responsible for removal of Plasmodium-infected erythrocytes in the liver. Moreover, there is increasing information, though controversially debated, that natural killer (NK) cells in the liver may also play a critical role in the elimination of Plasmodium-infected erythrocytes.
A study led by Prof. Marcos J. Araúzo-Bravo from Biodonostia in collaboration with researchers from Boeringer Ingelheim Pharma and Heinrich-Heine University, Germany, published in the journal of Vaccines, showed that (1) malaria-induced expansion of liver resident NK cells peaks on day 4 post infection in mice, (2) at this moment natural killer cell complex (NKC) of chromosome 6 is enriched with up-regulated genes in vaccinated mice, (3) the malaria-induced expansion is highly reduced by enhanced immigration of peripheral conventional NK cells, and (4) KLRB1F:CLEC2I interactions between NK cells and erythroid cells facilitate extramedullary erythroblastosis in the liver, thus critically contributing to vaccination-induced survival of otherwise lethal blood-stage malaria of Plasmodium chabaudi.
Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells
Araúzo-Bravo, M.J.; Delic, D.; Gerovska, D.; Wunderlich, F. Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells. Vaccines 2020, 8, 677. ; https://doi.org/10.3390/vaccines8040677