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

Patrick Waindok,Esther Wilk,Robert Geffers,Dimitri L Lindenwald,Christina Strube,Elisabeth Janecek-Erfurth,Klaus Schughart

doi:10.3390/microorganisms10010177

Abstract

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.

Highlights

The dog and cat roundworm Toxocara canis and Toxocara cati are globally occurring intestinal parasites with canids and felids as definitive hosts
As previously observed by Janecek et al [30], infected mice were exposed to varying degrees of clinical symptoms and neurobehavioral alterations. Alterations in both infection groups mainly started around day 6 pi with progressively increasing severity during the course of infection, T. cati-induced neurotoxocarosis was generally characterized by less severe clinical signs and neurobehavioral alterations
T. canis- and T. cati-induced neurotoxocarosis in the paratenic mouse model was associated with the comprehensive transcriptional alteration

Summary

Introduction

The dog and cat roundworm Toxocara canis and Toxocara cati are globally occurring intestinal parasites with canids and felids as definitive hosts. Infections in dogs and cats have been associated with a variety of pathologies, Microorganisms 2022, 10, 177. The global pooled prevalence of Toxocara infection in dogs is estimated at 11.1% and in cats at 17.0% [2,3], with significantly higher prevalences in young, rural, or stray animals. An estimated ≥100 million dogs and cats are infected and contaminate the environment with roundworm eggs [2,3]. A broad range of animals including humans can act as paratenic hosts after accidental ingestion of embryonated third-stage larvae (L3) containing eggs or L3 in tissues

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