Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria

Area of Science:

• Immunology
• Infectious Diseases
• Malariology

Background:

• CD8+ T cells have a dual role in Plasmodium falciparum malaria: protective in the liver stage and potentially pathogenic in the blood stage.
• The exact role of blood-stage CD8+ T cells in human malaria remains poorly understood.
• Cerebral malaria is a severe complication of P. falciparum infection.

Purpose of the Study:

• To investigate the role of CD8+ T cells and granzyme B in the blood-stage of human P. falciparum malaria.
• To compare CD8+ T cell phenotypes and granzyme B levels in children with different malaria infection statuses.

Main Methods:

• Cross-sectional study in Ghana involving children with complicated malaria, uncomplicated malaria, asymptomatic infection, and no infection.
• Measurement of plasma granzyme B levels.
• Flow cytometry analysis of CD8+ T cell phenotypes, including granzyme B expression and CD38 activation marker.

Main Results:

• Plasma granzyme B levels were significantly higher in children with febrile malaria compared to afebrile children.
• CD8+ T cells were the primary T cell subset expressing granzyme B.
• The proportion of granzyme B-expressing CD8+ T cells was significantly higher in children with complicated malaria than in those with uncomplicated malaria.
• CD38 expression on CD8+ T cells was similar across febrile malaria groups.

Conclusions:

• Elevated levels of cytotoxic CD8+ T cells (granzyme B+) in the blood suggest a pathogenic role in the development of severe malaria complications in humans.
• These findings highlight the complex involvement of CD8+ T cells in P. falciparum malaria pathogenesis.