Cargando…

Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations

Toxocara canis and Toxocara cati are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of Toxocara larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses...

Descripción completa

Detalles Bibliográficos
Autores principales: Waindok, Patrick, Janecek-Erfurth, Elisabeth, Lindenwald, Dimitri L., Wilk, Esther, Schughart, Klaus, Geffers, Robert, Strube, Christina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779660/
https://www.ncbi.nlm.nih.gov/pubmed/35056627
http://dx.doi.org/10.3390/microorganisms10010177
_version_ 1784637631450054656
author Waindok, Patrick
Janecek-Erfurth, Elisabeth
Lindenwald, Dimitri L.
Wilk, Esther
Schughart, Klaus
Geffers, Robert
Strube, Christina
author_facet Waindok, Patrick
Janecek-Erfurth, Elisabeth
Lindenwald, Dimitri L.
Wilk, Esther
Schughart, Klaus
Geffers, Robert
Strube, Christina
author_sort Waindok, Patrick
collection PubMed
description Toxocara canis and Toxocara cati are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of Toxocara larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses against Toxocara larvae are mostly unknown, whole-genome microarray transcription analysis was performed in cerebra and cerebella of experimentally infected C57Bl/6J mice as paratenic host model at days 14, 28, 70, 98, and 120 post-infection. Neuroinvasion of T. cati evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In T. canis-infected mice, 1039 cerebral and 2073 cerebellar DTGs were identified. Statistically significant dysregulations occurred in various pathways, including cholesterol biosynthesis, apoptosis signaling, and the Slit/Robo mediated axon guidance as well as different pathways associated with the immune and defense response. Observed dysregulations of the cholesterol biosynthesis, as well as the Alzheimer disease-amyloid secretase pathway in conjunction with previous histopathological neurodegenerative findings, may promote the discussion of T. canis as a causative agent for dementia and/or Alzheimer’s disease. Furthermore, results contribute to a deeper understanding of the largely unknown pathogenesis and host-parasite interactions during NT, and may provide the basis for prospective investigations evaluating pathogenic mechanisms or designing novel diagnostic and therapeutic approaches.
format Online
Article
Text
id pubmed-8779660
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87796602022-01-22 Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations Waindok, Patrick Janecek-Erfurth, Elisabeth Lindenwald, Dimitri L. Wilk, Esther Schughart, Klaus Geffers, Robert Strube, Christina Microorganisms Article Toxocara canis and Toxocara cati are globally occurring zoonotic roundworms of dogs and cats. Migration and persistence of Toxocara larvae in the central nervous system of paratenic hosts including humans may cause clinical signs of neurotoxocarosis (NT). As pathomechanisms of NT and host responses against Toxocara larvae are mostly unknown, whole-genome microarray transcription analysis was performed in cerebra and cerebella of experimentally infected C57Bl/6J mice as paratenic host model at days 14, 28, 70, 98, and 120 post-infection. Neuroinvasion of T. cati evoked 220 cerebral and 215 cerebellar differentially transcribed genes (DTGs), but no particular PANTHER (Protein ANalysis THrough Evolutionary Relationships) pathway was affected. In T. canis-infected mice, 1039 cerebral and 2073 cerebellar DTGs were identified. Statistically significant dysregulations occurred in various pathways, including cholesterol biosynthesis, apoptosis signaling, and the Slit/Robo mediated axon guidance as well as different pathways associated with the immune and defense response. Observed dysregulations of the cholesterol biosynthesis, as well as the Alzheimer disease-amyloid secretase pathway in conjunction with previous histopathological neurodegenerative findings, may promote the discussion of T. canis as a causative agent for dementia and/or Alzheimer’s disease. Furthermore, results contribute to a deeper understanding of the largely unknown pathogenesis and host-parasite interactions during NT, and may provide the basis for prospective investigations evaluating pathogenic mechanisms or designing novel diagnostic and therapeutic approaches. MDPI 2022-01-14 /pmc/articles/PMC8779660/ /pubmed/35056627 http://dx.doi.org/10.3390/microorganisms10010177 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Waindok, Patrick
Janecek-Erfurth, Elisabeth
Lindenwald, Dimitri L.
Wilk, Esther
Schughart, Klaus
Geffers, Robert
Strube, Christina
Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title_full Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title_fullStr Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title_full_unstemmed Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title_short Toxocara canis- and Toxocara cati-Induced Neurotoxocarosis Is Associated with Comprehensive Brain Transcriptomic Alterations
title_sort toxocara canis- and toxocara cati-induced neurotoxocarosis is associated with comprehensive brain transcriptomic alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779660/
https://www.ncbi.nlm.nih.gov/pubmed/35056627
http://dx.doi.org/10.3390/microorganisms10010177
work_keys_str_mv AT waindokpatrick toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT janecekerfurthelisabeth toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT lindenwalddimitril toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT wilkesther toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT schughartklaus toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT geffersrobert toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations
AT strubechristina toxocaracanisandtoxocaracatiinducedneurotoxocarosisisassociatedwithcomprehensivebraintranscriptomicalterations