Mouse neutrophils release extracellular traps in response to Naegleria fowleri

Abstract

Summary Naegleria fowleri is a free‐living amoeba, which is able to infect humans through the nasal mucosa causing a disease in the central nervous system known as primary amoebic meningoencephalitis (PAM). Polymorphonuclear cells (PMNs) play a critical role in the early phase of N fowleri infection. Recently, a new biological defence mechanism called neutrophil extracellular traps (NETs) has been attracting attention. These structures represent an important strategy to immobilize and kill invading microorganisms. In this work, we evaluate the capacity of N fowleri to induce the NETs release by PMNs cells in mice in vitro and in vivo. In vitro: Neutrophils from bone marrow were cocultured with N fowleri trophozoites. In vivo: we employed a mouse model of PAM. We evaluated DNA, histone and myeloperoxidase (MPO) and the formation of NETs by confocal microscopy. Our results showed N fowleri induce both NETs and MPO release by PMNs cells in mice after trophozoite exposure, which increased through time, in vitro and in vivo. These results demonstrate that NETs are somehow associated with the amoebas. We suggest PMNs release their traps trying to avoid N fowleri attachment at the apical side of the nasal epithelium.

The MPO system participates actively in the formation of an oxidative environment produced by neutrophils and activates the antioxidant mechanism of Naegleria fowleri

“…Previous studies have demonstrated that the NETs structures can bind and trap N. fowleri trophozoites. 42,48 However, it is important to consider that the amoeba produces an NETs. 49,50 This information could be useful to better understand the strategies that the amoeba has developed for its protection.…”

Three encephalitis-causing amoebae and their distinct interactions with the host

“…Neutrophilic inflammation and concurrent damage are abundant in PAM, and the neutrophils then produce extracellular traps (NETs) and secrete myeloperoxidase (MPO) (Figure 2D) [25][26][27][28]. NETs consist of DNA fibers that immobilize N. fowleri, whereas MPO damages N. fowleri as well as the surrounding cells.…”

The State of Art of Extracellular Traps in Protozoan Infections (Review)

“…A recent study evaluated the ability of N. fowleri to induce the release of NETs from mouse PMN cells in vitro and in vivo . The results showed that when PMNs and N. fowleri were cocultured, the parasites could induce the release of NETs and MPO from the neutrophils in a time- and dose-dependent manner ( 22 , 23 ). Because N. fowleri can infect humans through the nasal mucosa, if neutrophils are stimulated to release their ETs, N. fowleri may be damaged, and attachment to nasal mucosal cells may be prevented ( 22 ).…”

“…The results showed that when PMNs and N. fowleri were cocultured, the parasites could induce the release of NETs and MPO from the neutrophils in a time- and dose-dependent manner ( 22 , 23 ). Because N. fowleri can infect humans through the nasal mucosa, if neutrophils are stimulated to release their ETs, N. fowleri may be damaged, and attachment to nasal mucosal cells may be prevented ( 22 ). In addition, studies have shown that NETs cannot damage non-IgG-opsonized N. fowleri trophozoites but can damage human IgG-opsonized N. fowleri trophozoites.…”