A review of the proposed role of neutrophils in rodent amebic liver abscess models

Abstract

Host invasion by Entamoeba histolytica, the pathogenic agent of amebiasis, can lead to the development of amebic liver abscess (ALA). Due to the difficulty of exploring host and amebic factors involved in the pathogenesis of ALA in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings reveal that the chronic phase of ALA in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction. Hence, the present review discusses the possible role of neutrophils in the effector immune response in ALA in rodents. Properly activated neutrophils are probably successful in eliminating amebas through oxidative and non-oxidative mechanisms, including neutrophil degranulation, the generation of free radicals (O2−, H2O2, HOCl) and peroxynitrite, the activation of NADPH-oxidase and myeloperoxidase (MPO) enzymes, and the formation of neutrophil extracellular traps (NETs). On the other hand, if amebas are not eliminated in the early stages of infection, they trigger a prolonged and exaggerated inflammatory response that apparently causes ALAs. Genetic differences in animals and humans are likely to be key to a successful host immune response.

Entamoeba histolytica Trophozoites Induce a Rapid Non-classical NETosis Mechanism Independent of NOX2-Derived Reactive Oxygen Species and PAD4 Activity

“…Neutrophils have been implicated in defense against this parasite playing a crucial protective role (Asgharpour et al, 2005 ); nevertheless, involvement of neutrophils and other leukocytes in tissue damage has also been reported (Olivos-García et al, 2007 ). Oxidative (ROS production) and non-oxidative mechanisms are proposed to be used by neutrophils to kill amoeba (Ghosh et al, 2010 ; Pacheco-Yépez et al, 2011 ; Campos-Rodríguez et al, 2016 ). Mechanisms triggering neutrophils by amoebas are unknown but they could involve innate immune receptors such as TLRs.…”

Neutrophil extracellular traps and MPO in models of susceptibility and resistance against Entamoeba histolytica

“…The results suggest that the low expression of MPO in hamsters can decrease the presence of NETs (Figure 2), since this enzyme is a key element to induce the release of these traps. Some authors have suggested an important role for MPO against E histolytica , 2,11,35 and it is thought that differences in MPO concentration in the hamster and mouse can be crucial to eliminate the amoeba, since a previous work determined that MPO can be joined to the trophozoites of E histolytica and eliminate them 35 . In addition when we evaluated the amoeba viability (Figure 4) in the in vitro interactions using an MPO inhibitor (ABAH), the viability increased in comparison to that of 90‐min interaction group.…”

“…These two diseases are associated with significantly high levels of mortality worldwide 1 . Some authors have suggested that liver tissue damage observed in amoebic invasion is not directly related to amoebic mechanisms 2 …”

“…Moreover, previous studies reported that adequate activation of neutrophils favours the elimination of E histolytica through different mechanisms. On the other hand, inadequate activation and exacerbate inflammation enable ALA development 2 . Currently, the role of neutrophils in the formation or development of ALAs is unknown; nevertheless, the roles of the complement system and other cytotoxic molecules have been implicated 8 …”

Las citoquinas en el absceso hepático amebiano: un ejemplo de investigación inmunología en el ámbito clínico

“…El papel de estas citoquinas en el patógeno de los abscesos hepáticos amebianos necesita más investigación, particularmente para buscar otros factores de crecimiento, como TGF-b, HGF e IGF, y citoquinas reguladoras para elucidar sus roles durante las etapas crónicas del desarrollo de AHA. Varios estudios han demostrado la importancia de los neutrófilos en la respuesta innata contra la invasión de E. histolytica (52). Los neutrófilos activados proporcionan señales para la activación y maduración de los macrófagos, que a su vez liberan IL-1b, TNF-a, G-CSF y GM-CSF, de tal forma que estas citoquinas extienden la vida útil de los neutrófilos en los sitios de inflamación.…”