The potential link between the infections and the development of Alzheimer's disease (AD) has led to speculations about the role of various pathogens in triggering amyloid-β (Aβ) overproduction, possibly leading to AD onset. The globally distributed dog roundworm Toxocara canis was suggested to be a suitable candidate due to neurotropism of the larvae and infection chronicity. This study investigated whether chronic T. canis infection induces AD-like pathology in mice and whether Aβ is toxic to T. canis. BALB/c and APP/PS1 transgenic mice, which overproduce Aβ, were infected with T. canis L3 larvae and monitored for larval burden, Aβ accumulation, and behavioral changes. In vitro tests of recombinant Aβ toxicity against the larvae were also performed. Despite the presence of T. canis larvae in the central nervous system 8 and 16 weeks post-infection, no significant increase in Aβ concentration or AD-related behavioral alterations were observed. Aβ was detected on the surface and within the intestines of T. canis larvae, but in vitro exposure to recombinant Aβ did not affect larval viability or morphology. Our findings suggest that T. canis infection does not trigger AD-like pathology in mice, and Aβ does not act as an antiparasitic agent. This challenges the emerging hypothesis that chronic neurotoxocarosis infections may contribute to AD development.

TITLE: Absence de preuve de pathologie de la maladie d’Alzheimer chez les souris infectées par Toxocara canis. ABSTRACT: Le lien potentiel entre les infections et le développement de la maladie d’Alzheimer (MA) a suscité des spéculations sur le rôle de divers agents pathogènes dans le déclenchement de la surproduction de β-amyloïde (βA), pouvant conduire à l’apparition de la MA. Toxocara canis, un nématode du chien, répandu mondialement, a été suggéré comme un candidat potentiel en raison du neurotropisme de ses larves et de la chronicité de son infection. Cette étude examine si une infection chronique à T. canis induit une pathologie de type MA chez la souris et si la βA est toxique pour T. canis. Des souris transgéniques BALB/c et APP/PS1, qui surproduisent la βA, ont été infectées par des larves L3 de T. canis et la charge larvaire, l’accumulation de βA et les changements comportementaux ont été étudiés. Des tests in vitro de toxicité de la βA recombinante contre les larves ont également été réalisés. Malgré la présence de larves de T. canis dans le système nerveux central 8 et 16 semaines après l’infection, aucune augmentation significative de la concentration de la βA ni d’altération comportementale liée à la MA n’ont été observées. La βA a été détectée à la surface et dans les intestins des larves de T. canis, mais l’exposition in vitro à la βA recombinante n’a pas affecté la viabilité ou la morphologie des larves. Nos résultats suggèrent que l’infection à T. canis ne déclenche pas de pathologie de type MA chez la souris, et que la βA n’agit pas comme agent antiparasitaire. Cela remet en cause l’hypothèse émergente selon laquelle les infections chroniques par neurotoxocarose pourraient contribuer au développement de la MA.

• Klíčová slova
• Alzheimer’s disease, Amyloid-β, Infectious hypothesis, Neurotoxocarosis, Toxocara canis,
• MeSH
• Alzheimerova nemoc * patologie   parazitologie   etiologie   MeSH
• amyloidní beta-protein toxicita   metabolismus   analýza   MeSH
• larva MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši transgenní MeSH
• myši MeSH
• psi MeSH
• střeva parazitologie   MeSH
• Toxocara canis * fyziologie   růst a vývoj   MeSH
• toxokaróza * komplikace   patologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amyloidní beta-protein MeSH

Toxocara canis larvae are one of the most overlooked agents of nervous system infection in paratenic hosts. Previous studies in mouse models have shown that infection with various (mainly high) numbers of larvae leads to neurobehavioral disturbances and pathological changes. Our study investigated whether the infection with low and moderate numbers of larvae could affect the physical condition, motor skills, and pathogenesis in the brains of experimentally infected mice.Two groups of BALB/c mice were orally infected with 10 and 100 T. canis larvae per animal and examined regularly until the 97th week after infection. General appearance, specific antibody responses, and motor/balance skills were assessed. The number and viability of larvae in the liver, spleen, lungs, and brain were assessed by quantitative compressed biopsy technique, while the pathological changes of the brain infection were studied histologically.As a result, changes were observed in overall appearance, activity, as well as motor and balance ability. The infections were associated with an increased IgG antibody response to the specific anti-T. canis excretory/secretory antigen and tissue damage in the brain characterized by necrosis, cell infiltrations, including foamy cells, and hemorrhages.The study demonstrated the effects of low and moderate T. canis infection in a paratenic host during the chronic phase of infection, which lasted up to 97 weeks for the first time.

• Klíčová slova
• Toxocara canis, Mice, Moderate to low inoculum, Neurobehavioral disorders, Pathological changes,
• MeSH
• chování zvířat MeSH
• imunoglobulin G krev   MeSH
• játra parazitologie   patologie   MeSH
• larva * MeSH
• modely nemocí na zvířatech MeSH
• mozek * parazitologie   patologie   MeSH
• myši inbrední BALB C * MeSH
• myši MeSH
• protilátky helmintové krev   MeSH
• Toxocara canis * MeSH
• toxokaróza * parazitologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin G MeSH
• protilátky helmintové MeSH

The amyloid cascade hypothesis, focusing on pathological proteins aggregation, has so far failed to uncover the root cause of Alzheimer's disease (AD), or to provide an effective therapy. This traditional paradigm essentially explains a mechanism involved in the development of sporadic AD rather than its cause. The failure of an overwhelming majority of clinical studies (99.6%) demonstrates that a breakthrough in therapy would be difficult if not impossible without understanding the etiology of AD. It becomes more and more apparent that the AD pathology might originate from brain infection. In this review, we discuss a potential role of bacteria, viruses, fungi, and eukaryotic parasites as triggers of AD pathology. We show evidence from the current literature that amyloid beta, traditionally viewed as pathological, actually acts as an antimicrobial peptide, protecting the brain against pathogens. However, in case of a prolonged or excessive activation of a senescent immune system, amyloid beta accumulation and aggregation becomes damaging and supports runaway neurodegenerative processes in AD. This is paralleled by the recent study by Alam and colleagues (2022) who showed that alpha-synuclein, the protein accumulating in synucleinopathies, also plays a critical physiological role in immune reactions and inflammation, showing an unforeseen link between the 2 unrelated classes of neurodegenerative disorders. The multiplication of the amyloid precursor protein gene, recently described by Lee and collegues (2018), and possible reactivation of human endogenous retroviruses by pathogens fits well into the same picture. We discuss these new findings from the viewpoint of the infection hypothesis of AD and offer suggestions for future research.

• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• amyloidový prekurzorový protein beta metabolismus   MeSH
• antibakteriální látky terapeutické užití   MeSH
• antiinfekční látky * metabolismus   MeSH
• lidé MeSH
• mozek patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• amyloidový prekurzorový protein beta MeSH
• antibakteriální látky MeSH
• antiinfekční látky * MeSH

Toxocara canis, a gastrointestinal parasite of canids, is also highly prevalent in many paratenic hosts, such as mice and humans. As with many other helminths, the infection is associated with immunomodulatory effects, which could affect other inflammatory conditions including autoimmune and allergic diseases. Here, we investigated the effect of T. canis infection on the course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Mice infected with 2 doses of 100 T. canis L3 larvae 5 weeks prior to EAE induction (the Tc+EAE group) showed higher EAE clinical scores and greater weight loss compared to the non-infected group with induced EAE (the EAE group). Elevated concentrations of all measured serum cytokines (IL-1α, IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) were observed in the Tc+EAE group compared to the EAE group. In the CNS, the similar number of regulatory T cells (Tregs; CD4+FoxP3+Helios+) but their decreased proportion from total CD4+ cells was found in the Tc+EAE group compared to the EAE group. This could indicate that the group Tc+EAE harboured significantly more CD4+ T cells of non-Treg phenotype within the affected CNS. Altogether, our results demonstrate that infection of mice with T. canis worsens the course of subsequently induced EAE. Further studies are, therefore, urgently needed to reveal the underlying pathological mechanisms and to investigate possible risks for the human population, in which exposure to T. canis is frequent.

• Klíčová slova
• EAE, MOG, Toxocara canis, experimental autoimmune encephalomyelitis, helminth, multiple sclerosis,
• MeSH
• CD4-pozitivní T-lymfocyty patologie   MeSH
• cytokiny MeSH
• encefalomyelitida autoimunitní experimentální * patologie   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• roztroušená skleróza * patologie   MeSH
• Toxocara canis * MeSH
• toxokaróza * komplikace   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH

BACKGROUND: Larval toxocarosis (LT), a zoonotic disease transmitted by dogs, cats, and other carnivores, is caused by roundworms of the genus Toxocara. Humans become infected by ingesting embryonated eggs of this parasite. In this study, we present data on the seroprevalence of LT in the Czech Republic collected by the National Reference Laboratory for Tissue Helminthoses in 2012-2016. METHODS: Using enzyme-linked immunosorbent assay, a total of 4428 adults and children with or without clinical symptoms were examined for the presence of IgG antibodies against Toxocara canis excretory-secretory antigens. RESULTS: Of all the persons examined, specific Toxocara antibodies were detected in 160 (3.6%) individuals. There were, however, significant differences between various regions, with seropositivity rates ranging from 1.4 to 7.5%. CONCLUSION: In comparison to studies from 1998 and 2004, our results suggest a decrease in overall Toxocara seroprevalence in the Czech population, whereby the rates are similar to or even lower than rates in some other Central European countries.

• Klíčová slova
• Czech Republic, Seroprevalence, Toxocara canis, Toxocara cati, Toxocarosis, Zoonosis,
• MeSH
• dítě MeSH
• dospělí MeSH
• ELISA MeSH
• imunoglobulin G krev   MeSH
• kojenec MeSH
• larva MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• protilátky helmintové krev   MeSH
• senioři MeSH
• séroepidemiologické studie MeSH
• Toxocara izolace a purifikace   MeSH
• toxokaróza krev   epidemiologie   MeSH
• zoonózy epidemiologie   parazitologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• imunoglobulin G MeSH
• protilátky helmintové MeSH