Towards a vaccine against asexual blood stage infection by Plasmodium falciparum

ABSTRACT The var genes encode Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins, a set of highly diverse surface-expressed proteins that mediate adhesion of erythrocytes infected with asexual blood-stage parasites to host endothelium. Switching among expressed PfEMP1 variants in the course of a blood-stage infection is a key component of antigenic variation, and thus immune evasion, by the parasite. The majority of var loci are found in the subtelomeric regions of P. falciparum chromosomes associated with members of other multigene families, including stevor. Both PfEMP1 and STEVOR are expressed in gametocytes, the transmissible parasite stage, but the role of these proteins in the biology of sexual-stage parasites remains unknown. PfEMP1 may continue to mediate antigenic variation in gametocytes, which need to persist in the host for many days before reaching maturity. Using quantitative reverse transcription-PCR and Northern hybridization, we demonstrate that transcription of a defined subset of type C var loci occurs during gametocyte development in vitro. This transcriptional program occurs in gametocytes regardless of the var expression phenotype of their asexual progenitors and therefore is subject to regulatory processes distinct from those that manage antigenic variation in the asexual parasite. In contrast, the same stevor variants are transcribed in both gametocytes and their asexual progenitors. We also provide evidence that for both asexual parasites and gametocytes, var and stevor transcription patterns are not linked to each other.

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The Antigen-Presenting Potential of Vγ9Vδ2 T Cells During Plasmodium falciparum Blood-Stage Infection

The Journal of Infectious Diseases ◽

10.1093/infdis/jix149 ◽

2017 ◽

Vol 215 (10) ◽

pp. 1569-1579 ◽

Cited By ~ 12

Author(s):

Jennifer Howard ◽

Séverine Loizon ◽

Christopher J. Tyler ◽

Dorothée Duluc ◽

Bernhard Moser ◽

...

Keyword(s):

T Cells ◽

Plasmodium Falciparum ◽

Blood Stage ◽

Blood Stage Infection ◽

Vγ9vδ2 T Cells ◽

Antigen Presenting ◽

Stage Infection

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Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection

Malaria Journal ◽

10.1186/s12936-019-2962-0 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Damian A. Oyong ◽

Jessica R. Loughland ◽

Arya SheelaNair ◽

Dean Andrew ◽

Fabian D. L. Rivera ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Red Blood Cells ◽

Blood Cells ◽

Blood Stage ◽

Regulatory Proteins ◽

Complement Regulatory Proteins ◽

Blood Stage Infection ◽

Low Levels ◽

Stage Infection ◽

Blood Stage Malaria

Abstract Background Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection. Methods The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated. Results CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM. Conclusions Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

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