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Histopathological characterization of Toxocara canis- and T. cati-induced neurotoxocarosis in the mouse model

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Abstract

Infective larvae of Toxocara canis and T. cati, the common roundworms of dogs and cats, may invade the central nervous system of paratenic hosts, including humans, causing neurotoxocarosis (NT). Previous studies on NT in the model organism “mouse” have indicated distinct differences between T. canis and T. cati regarding larval migration patterns as well as the severity of clinical symptoms and behavioural alterations. The objective of the present study was to provide an extensive characterization of the underlying histopathological alterations, comparing T. canis- and T. cati-induced changes in different brain areas over the course of murine infection. Four histological sections of five brains each of T. canis- and T. cati-infected as well as uninfected C57Bl/6 mice were investigated 7, 14, 28, 42, 70 and 98 days post infection (dpi), while brains of T. cati-infected and control mice were also available 120 and 150 dpi. In addition to haematoxylin-eosin and luxol fast blue-cresyl violet staining, immunohistochemistry was employed to study microglia/macrophage cell morphology and to detect accumulation of β-amyloid precursor protein (β-APP) as an indicator of axonal damage. Haemorrhages, eosinophilic vasculitis and activated microglia/macrophages were detected in both infection groups starting 7 dpi, followed by eosinophilic meningitis in cerebra as from 14 dpi. Overall, little differences in the proportion of animals affected by these alterations were found between the two infection groups. In contrast, the proportion of animals displaying β-APP accumulation was significantly higher in the T. canis than T. cati group as from 28 dpi regarding the cerebrum as well as at 98 dpi regarding the cerebellum. In T. canis-infected mice, myelinophagic microglia/macrophages (“gitter cells”) appeared as from 14 dpi, whereas these were first observed at 70 dpi in T. cati-infected animals. The proportion of animals displaying demyelination and/or gitter cells in the cerebrum was significantly higher in the T. canis than T. cati group as from 28 dpi, and at 28 and 42 dpi regarding the cerebellum. Earlier and more severe neurodegeneration during T. canis- than T. cati-induced NT, especially in the cerebrum, may explain the differences in behavioural alterations observed in previous studies. In addition to differences in larval migration preferences, immunological processes may contribute to these patterns, which warrant further investigation.

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Abbreviations

ABC:

avidin-biotin-peroxidase

BSA:

bovine serum albumin

β-APP:

β-amyloid precursor protein

dpi:

day post infection

H&E:

haematoxylin-eosin

LFB:

luxol fast blue-cresyl violet

PBS:

phosphate-buffered saline

pi:

post infection

NT:

neurotoxocarosis

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Acknowledgements

The authors wish to thank Fred Lühder for valuable comments on the manuscript and Solveig Blumenbecker and Sabine Händel for excellent technical assistance.

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Author notes

  1. Lea Heuer

    Present address: Bayer Animal Health, Alfred-Nobel-Str. 50, 40789, Monheim am Rhein, Germany

  2. Elisabeth Janecek-Erfurth

    Present address: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hanover Medical School and the Helmholtz Centre for Infection Research, 30625, Hannover, Germany

Authors and Affiliations

  1. Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hanover, Germany

    Andrea Springer, Lea Heuer, Elisabeth Janecek-Erfurth & Christina Strube

  2. Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559, Hanover, Germany

    Andreas Beineke

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  1. Andrea Springer
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Correspondence to Christina Strube.

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Springer, A., Heuer, L., Janecek-Erfurth, E. et al. Histopathological characterization of Toxocara canis- and T. cati-induced neurotoxocarosis in the mouse model. Parasitol Res 118, 2591–2600 (2019). https://doi.org/10.1007/s00436-019-06395-7

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  • DOI: https://doi.org/10.1007/s00436-019-06395-7

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