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Mechanisms of the host immune response and helminth-induced pathology during Trichobilharzia regenti (Schistosomatidae) neuroinvasion in mice.
- Source :
-
PLoS pathogens [PLoS Pathog] 2022 Feb 04; Vol. 18 (2), pp. e1010302. Date of Electronic Publication: 2022 Feb 04 (Print Publication: 2022). - Publication Year :
- 2022
-
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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Biomarkers metabolism
Chemokines metabolism
Disease Models, Animal
Female
Gene Expression Profiling
Host-Parasite Interactions
Immunity
Major Histocompatibility Complex
Mice
Mice, Inbred C57BL
Neuroglia parasitology
Neurons parasitology
Trematode Infections pathology
Arginase metabolism
Eosinophils metabolism
Schistosomatidae immunology
Spinal Cord parasitology
Trematode Infections immunology
Trematode Infections metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 18
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 35120185
- Full Text :
- https://doi.org/10.1371/journal.ppat.1010302