Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice

Abstract

Helminth neuroinfections represent serious medical conditions, but the diversity of the host-parasite interplay within the nervous tissue often remains poorly understood, partially due to the lack of laboratory models. Here, we investigated the neuroinvasion of the mouse spinal cord by Trichobilharzia regenti (Schistosomatidae). Active migration of T. regenti schistosomula through the mouse spinal cord induced motor deficits in hindlimbs but did not affect the general locomotion or working memory. Histological examination of the infected spinal cord revealed eosinophilic meningomyelitis with eosinophil-rich infiltrates entrapping the schistosomula. Flow cytometry and transcriptomic analysis of the spinal cord confirmed massive activation of the host immune response. Of note, we recorded striking upregulation of the major histocompatibility complex II pathway and M2-associated markers, such as arginase or chitinase-like 3. Arginase also dominated the proteins found in the microdissected tissue from the close vicinity of the migrating schistosomula, which unselectively fed on the host nervous tissue. Next, we evaluated the pathological sequelae of T. regenti neuroinvasion. While no demyelination or blood-brain barrier alterations were noticed, our transcriptomic data revealed a remarkable disruption of neurophysiological functions not yet recorded in helminth neuroinfections. We also detected DNA fragmentation at the host-schistosomulum interface, but schistosomula antigens did not affect the viability of neurons and glial cells in vitro. Collectively, altered locomotion, significant disruption of neurophysiological functions, and strong M2 polarization were the most prominent features of T. regenti neuroinvasion, making it a promising candidate for further neuroinfection research. Indeed, understanding the diversity of pathogen-related neuroinflammatory processes is a prerequisite for developing better protective measures, treatment strategies, and diagnostic tools.

Simplifying Schistosome Surveillance: Using Molecular Cercariometry to Detect and Quantify Cercariae in Water

“…Avian schistosomes are considered an inconvenience and a public health nuisance due to their ability to cause swimmer’s itch [ 1 , 18 , 19 ]. However, research revealed that they may be a larger public health issue than once thought, as one species, Trichobilharzia regenti , can enter the central nervous system of mice [ 20 , 21 ]. Schistosomulae were found within the spinal cords, brain stems, and cerebellums of mice [ 20 , 21 ], along with the medulla oblongata [ 20 ], and infected mice were observed to have decreased motor functions [ 20 , 21 ].…”

“…However, research revealed that they may be a larger public health issue than once thought, as one species, Trichobilharzia regenti , can enter the central nervous system of mice [ 20 , 21 ]. Schistosomulae were found within the spinal cords, brain stems, and cerebellums of mice [ 20 , 21 ], along with the medulla oblongata [ 20 ], and infected mice were observed to have decreased motor functions [ 20 , 21 ]. It has been considered that not all avian schistosome cercariae are able to penetrate human skin, or if they can, they then die within the skin (causing the dermatitis) [ 1 ].…”

“…It has been considered that not all avian schistosome cercariae are able to penetrate human skin, or if they can, they then die within the skin (causing the dermatitis) [ 1 ]. Now, with the information provided by researchers on the ability of T. regenti to invade the central nervous system of mice [ 20 , 21 ], further studies are critical to determine the fate of other species of avian schistosomes after penetrating human skin.…”

The neurotropic schistosome vs experimental autoimmune encephalomyelitis: are there any winners?

“…Mice were anaesthetized with Isoflurin (Vetpharma Animal Health, Barcelona, Spain) and transcardially perfused with phosphate-buffered saline (PBS). Cell suspension from the entire CNS was prepared according to Macháček et al (2022). Briefly, the tissue was extracted, gently mechanically homogenized and filtered through a 70 μm cell strainer.…”

“…Given that T. regenti is found mostly in the white matter up to 21 days post-infection (Macháček et al, 2020(Macháček et al, , 2022, we quantified its myelination and cell infiltration in 1000 LT mice as possible factors contributing to pathology. Representative photos of the spinal cord sections are shown in Fig.…”