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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1493946
This article is part of the Research Topic Neutrophil Extracellular Traps (NETs) Triggered by Helminths and Protozoan Parasites View all articles

Entamoeba histolytica-induced NETs are highly cytotoxic on hepatic and colonic cells due to serine proteases and myeloperoxidase activities

Provisionally accepted
Fabian Jorge-Rosas Fabian Jorge-Rosas 1César Díaz-Godínez César Díaz-Godínez 1Samuel García-Aguirre Samuel García-Aguirre 1Santiago Martínez-Calvillo Santiago Martínez-Calvillo 2Julio César Carrero Julio César Carrero 1*
  • 1 Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City, Mexico
  • 2 Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala. Universidad Nacional Autónoma de México, Ciudad de México, Mexico

The final, formatted version of the article will be published soon.

    During intestinal and liver invasion by the protozoan parasite Entamoeba histolytica, extensive tissue destruction linked to large neutrophil infiltrates is observed. It has been proposed that microbicidal components of neutrophils are responsible for the damage, however, the mechanism by which they are released and act in the extracellular space remains unknown. In previous studies, we have shown that E. histolytica trophozoites induce NET formation, leading to the release of neutrophil granule content into extruded DNA. In this work, we evaluate the possible participation of NETs in the development of amoeba-associated pathology and analyze the contribution of anti-microbial components of the associated granules. E. histolytica-induced NETs were isolated and their effect on the viability and integrity of HCT 116 colonic and Hep G2 liver cultures were evaluated. The results showed that simple incubation of cell monolayers with purified NETs for 24 h resulted in cell detachment and death in a dose-dependent manner. The effect was thermolabile and correlated with the amount of DNA and protein present in NETs. Pretreatment of NETs with specific inhibitors of some microbicidal components suggested that serine proteases, are mostly responsible for the damage caused by NETs in HCT 116 cells, while the MPO activity was the most related to Hep G2 cells damage. Our study also points to a very important role of DNA as a scaffold for the activity of these proteins. We show evidence of the development of NETs in amoebic liver abscesses in hamsters as a preamble to evaluate their participation in tissue damage. In conclusion, these studies demonstrate that amoebic-induced NETs have potent cytotoxic effects on target cells and, therefore, may be responsible for the intense damage associated with tissue invasion by this parasite.

    Keywords: Entamoeba histolytica, NETs, Neutrophils, Cell damage, HCT 116, Hep G2, extracellular vesicles

    Received: 10 Sep 2024; Accepted: 14 Nov 2024.

    Copyright: © 2024 Jorge-Rosas, Díaz-Godínez, García-Aguirre, Martínez-Calvillo and Carrero. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Julio César Carrero, Institute of Biomedical Research, National Autonomous University of Mexico, Mexico City, Mexico

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