Extracellular Killing of Trypanosoma cruzi Amastigotes by Human Eosinophils1

Abstract

Granules released from human eosinophils upon interaction with Trypanosoma cruzi amastigotes in vitro were seen attached to the surface of non-internalized parasites by electron microscopy. Amastigote damage was preceded by the binding of eosinophil granule material to its membrane, and eosinophil granule major basic protein (MBP) bound to the parasite surface was readily detectable. Additional evidence of eosinophil cytotoxicity for extracellular amastigotes was the observation that amastigotes trapped between two eosinophils, without being ingested by either one, were destroyed at the interface. Amastigotes isolated from the spleens of infected mice or grown in culture were similarly sensitive to the lytic effects of purified MBP. These results demonstrate the ability of human eosinophils to lyse T. cruzi amastigotes extracellularly in the absence of antibody and suggest that MBP may be involved in the effect. Thus, eosinophils, known to be capable of destroying phagocytosed amastigotes, could also contribute to the clearance of these parasites through extracellular killing.

The effect of cationic charge on release of eosinophil mediators

“…7,[37][38][39][40] Opsonized helminth parasites, targeted by eosinophils, acquire eosinophil-derived cationic proteins on their surface. 41,42 Eosinophil adhesion to and killing of parasitic worm targets is greatly enhanced if the worm surface is coated with MBP. 8 Heparin blocks helminthic parasite killing in vitro.…”

Post-translational Tyrosine Nitration of Eosinophil Granule Toxins Mediated by Eosinophil Peroxidase

“…In response to allergen provocation or parasitic infection, expanded eosinophil populations from the bone marrow are selectively recruited to affected tissues (1). The release of cationic toxins from activated eosinophils by degranulation is regarded as a dominant effector function of these cells, mediating lysis of helminths and protozoae (7)(8)(9)(10). The positive net charge conveys tight toxin binding to negatively charged cell surfaces where EPO causes oxidation of membrane components in the presence of hydrogen peroxide (H 2 O 2 ) (8).…”

Antimicrobial activity of human eosinophil granule proteins: involvement in host defence against pathogens

“…Upon infection by T. cruzi, eosinophil degranulation was observed, and MBP was detected bound to the surface of the protozoa ultimately, resulting in amastigote damage (Villalta & Kierszenbaum, 1984;Kierszenbaum et al, 1986;Villalta et al, 1987). All the eosinophil granule proteins were found to be toxic to Trypanosoma amastigotes and trypomastigotes obtained from blood, cell cultures, or insect vectors (Molina et al, 1988).…”