CD8+ T cell activation by murine erythroblasts infected with malaria parasites

Abstract

Recent studies show that some human malaria parasite species Plasmodium falciparum and P. vivax parasitize erythroblasts; however, the biological and clinical significance of this is unclear. To investigate further, we generated a rodent malaria parasite (P. yoelii 17XNL) expressing GFP-ovalbumin (OVA). Its infectivity to erythroblasts was confirmed, and parasitized erythroblasts were capable of initiating malaria infections. Experiments showed that MHC class I molecules were highly expressed on parasitized erythroblasts. As CD8+ T cells recognize MHC class I and peptide complexes on target cells, and are involved in protection or pathology against malaria, we examined whether erythroblasts are targeted by CD8+ T cells. Purified non-parasitized erythroblasts pulsed with OVA peptides were recognized by OVA-specific CD8+ T cells. Crucially, parasitized erythroblasts isolated from GFP-OVA-, but not GFP- infected-mice, activated OT-I CD8+ T cells, indicating that CD8+ T cells recognize parasitized erythroblasts in an antigen-specific manner.

Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution

“…Moreover, the level of H2 K expression on P. yoelii 17X infected cells from mice of different strains correlates with the ability of each strain to control the infection (Jayawardena et al, 1983). More recently, it has been shown that malaria parasites can parasitize erythroblasts, which have high levels of MHC class I molecules and the capacity to activate CD8+ T cells (Imai et al, 2013). Importantly, H2 K and H2 D molecules were present in exPy (Martin-Jaular et al, 2011) and rexPy (Dataset S3).…”

PD-1 Deficiency Enhances Humoral Immunity of Malaria Infection Treatment Vaccine

“…Recently, evidence has shown that parasitized erythroblast could activate CD8 ϩ T cells (26). Although CD8 ϩ T cells were found to be dispensable for the protective effect of ITV-immunized mice against blood-stage challenge (7), it is protective in the immunized mice that survived infection with both P. yoelii XNL and, subsequently, P. yoelii 17XL (27).…”

Plasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential

“…This is in contrast to mature erythrocytes that have completely lost expression of MHC molecules. Previous work using a genetically engineered mouse model of murine malaria has shown that CD8 + T cells can be activated by parasitized erythroblasts but not parasitized mature red blood cells through MHC-I dependent mechanisms [16]. Thus, we hypothesize that the higher proportion of infected reticulocytes in P .…”