Effects of cytokines, complement, and antibody on the neutrophil respiratory burst and phagocytic response to Plasmodium falciparum merozoites

Abstract

The interaction between Plasodium falciparum merozoites and human neutrophils, as well as the role of cytokines, complement, and antimalarial antibody on this interaction, was examined in vitro by measuring luminol-dependent chemiluminescence and phagocytosis. Merozoites, in the presence of heat-inactivated (56°C/30 min) normal serum, had very little effect on the neutrophil chemiluminescence. This response was significantly enhanced by the addition of normal serum (containing normal complement activity). In the presence of serum or plasma containing anti-P. falciparum antibodies (IS) with no detectable complement activity, the merozoites induced a marked response characterized by an increase in initial peak rate of chemiluminescence and a sustained increased rate of chemiluminescence. However, this response was not further increased if IS containing complement activity was used. Pretreatment of neutrophils with either tumor necrosis factor alpha, lymphotoxin, or gamma interferon significantly increased the neutrophil response to IS-treated merozoites, reflected in an increased initial peak rate and sustained increased rate of chemiluminescence. The effects of cytokine treatment of neutrophils and IS opsonization of merozoites were synergistic. In association with the changes in the chemiluminescence responses, IS was shown to promote phagocytosis of merozoites by neutrophils, and this event was further increased by treating neutrophils with the cytokines. The results emphasize the importance of antibody and cytokines in neutrophil-mediated damage of P. fakciparum merozoites.

Interferon‐γ activation of polymorphonuclear neutrophil function

“…Short-term treatment of PMNs with IFN-c (20-30 min) was shown by Shalaby et al to increase the phagocytosis of latex beads 75 and other studies demonstrated increased phagocytosis of Plasmodium falciparum merozoites induced by IFN-c treatment. 76 Studies with IFN-c knockout mice have also demonstrated that PMNs from these mice exhibit a twofold reduction in phagocytosis. Because the primary function of PMNs is to damage and destroy foreign microbes, numerous studies have investigated how IFN-c treatments modulate this ability.…”

Antigenicity of Recombinant Proteins Derived from Rhoptry-Associated Protein 1 of Plasmodium falciparum

“…The subclass of IgG antibodies is likely to be an important factor modulating cellular immunity to malaria. Cytophilic IgG1 and IgG3 antibodies that bind to receptors on monocytes, macrophages, and neutrophils enhance antiparasite mechanisms, including phagocytosis (11,23), antibody-dependent cellular inhibition (3), and respiratory burst in vitro (24). In vivo, the presence of IgG1 and IgG3 antibodies has been correlated with individuals' ability to maintain low parasite densities (1,2,12).…”

Complement Resistance of Parasites

“…Trichomonas vaginalis and Giardia lamblia) have been shown to activate the C system. The possible modes of C resistance of these parasites have been largely unexplored, although some mechanisms have been suggested for at least Plasmodium falciparum [66] and Trichomonas vaginalis [67].…”