Circulating concentrations of soluble granzyme A and B increase during natural and experimental Plasmodium falciparum infections

Abstract

SUMMARYRelease of soluble Granzymes (sGranzymes) is considered to reflect activation of cytotoxic T lymphocytes and NK cells. sGranzymes and a number of pro-inflammatory cytokines were measured in plasma of malaria patients with natural or experimentally induced Plasmodium falciparum infections. Concentrations of sGranzyme A and B, IL-10, IL-12p70 and CRP were significantly increased in African children presenting with clinical malaria; IL-10 and CRP concentrations were significantly correlated with disease severity. In nonimmune Dutch volunteers which were experimentally infected by P. falciparuminfected mosquitoes, sGranzyme A increment started 1-2 days prior to clinical symptoms and microscopically detectable parasitaemia. This coincided with increases in IFN g , IL-12p40 and IL-8, while sGranzyme B and IL-10 levels increased 24-48 h later. The elevation of sGranzyme A and IFN g in nonimmune volunteers suggests that NK cells are activated upon release of parasites by infected liver cells and subsequently during blood stage infection; thus, NK cells are likely involved innate immune human host resistance in the early phase of a malaria infection.

Effect of malaria components on blood mononuclear cells involved in immune response

“…In Malawian children with severe malaria, mortality was observed to increase with increasing serum TNF-α [31] , and in plasma of African children, TNF-α levels were found to be higher among those with cerebral malaria (CM) than in those with uncomplicated P. falciparum malaria [23] . A recent experiment involving P. falciparum infection in malaria-naive individuals has shown a coordinated increase in the level of pro-inflammatory cytokines, including IFN-γ, IL-12, and IL-8, in serum at the time when parasite emergence from the liver and the first appearance of parasitized erythrocytes [32] . In vitro studies have demonstrated that PRBCs can induce the production of TNF-α, IL-12, and IFN-γ by PBMCs of naive donors within 10 h [33] .…”

Cellulesnatural killeret immunité innée contre le paludisme

“…La production d'IL18 serait également un élément important de la réponse immunitaire contre le parasite [12][13][14]. De plus, au cours du paludisme de l'enfant, les concentrations de granzymes A et B solubles, ainsi que des cytokines (IL-12p70, IL-10), sont augmentées dans le sérum [15]. Par ailleurs, la réponse immunitaire précoce a été étudiée chez des volontaires sains non immuns infectés par une souche de Pf étendue à plusieurs autres souches de Pf, y compris certains isolats cliniques [20].…”

Extracellular Matrix Remodeling by Human Granzyme B via Cleavage of Vitronectin, Fibronectin, and Laminin

“…Plasma granzymes are also elevated during viral infections (human immunodeficiency virus-1, Epstein-Barr virus) and certain bacterial infections (16,18,19). These extracellular granzymes may arise via constitutive (nonspecific) secretion after CLs degranulate (20) or may escape the immunological synapse as the CL degranulates, disengages, and moves onto another target (21,22).…”