Analysis of innate defences against Plasmodium falciparum in immunodeficient mice

NOD/SCID mice undergoing an immunomodulatory protocol that includes, clodronate-loaded liposomes to deplete macrophages and an anti-polymorphonuclear leukocytes antibody, were grafted with human red blood cells and P. falciparum. The systematic and kinetic analysis of the remaining innate immune responses included the number and phenotype of peripheral blood leukocytes as well as inflammatory cytokines/chemokines released in periphery. The innate responses towards the murine parasite Plasmodium yoelii were used as a control.Results show that 1) P. falciparum induces a strong inflammation characterized by an increase in circulating leukocytes and the release of inflammatory cytokines; 2) in contrast, the rodent parasite P. yoelii, induces a far more moderate inflammation; 3) human red blood cells and the anti-inflammatory agents employed induce low-grade inflammation; and 4) macrophages seem to bear the most critical function in controlling P. falciparum survival in those mice, whereas polymorphonuclear and NK cells have only a minor role.Despite the use of an immunomodulatory treatment, immunodeficient NOD/SCID mice are still able to mount substantial innate responses that seem to be correlated with parasite clearance. Those results bring new insights on the ability of innate immunity from immunodeficient mice to control xenografts of cells of human origin and human pathogens.Defences against foreign cells, including pathogens, rely on both innate or non-adaptive responses, and adaptive or antigen-specific immune responses. However, modern immunology has focused primarily or almost exclusively on the latter.Therefore, various strains of mice having a genetic deficiency in cells responsible for adaptive immunity (i.e. T and B lymphocytes) have been selected, which have been used for the grafting of xenogenic cells, particularly those of a human origin. Indeed, the vast majority of these studies have focused on the grafting of human lymphocytes, haematopoietic stem ce