Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection.
Citations
Citations to this article as recorded by
Toxocara canis infections in mice: from subtle to severe consequences in 100 weeks Nicol Bernardová, Jan Novák, Chia-Kwung Fan, Libuše Kolářová, Marta Chanová Journal of Helminthology.2025;[Epub] CrossRef
Using Biocontrol Fungi to Control Helminthosis in Wild Animals: An Innovative Proposal for the Health and Conservation of Species Júlia dos Santos Fonseca, Beatriz Bacelar Barbosa, Adolfo Paz Silva, María Sol Arias Vázquez, Cristiana Filipa Cazapal Monteiro, Huarrisson Azevedo Santos, Jackson Victor de Araújo Pathogens.2025; 14(8): 775. CrossRef
The potential relationship between Toxocara canis infection and epilepsy in a rat model Amina M. Salama, Dina I. Elgendy, Rasha A. Elmahy, Asmaa F. Eltantawy, Monira A. Seleem, Ahmed M. Elgohary, Omaima K. Docmac, Marwa E. F. Al Mwafy, Ahmed A. Almeldin, Mahmoud S. Sharaf Parasitology Research.2025;[Epub] CrossRef
Efficacy of artemether against toxocariasis in mice: parasitological and immunopathological changes in brain, liver, and lung Dina I. Elgendy, Rasha A. Elmahy, Alaa Ibrahim Mohamed Amer, Hoda A. Ibrahim, Asmaa Fawzy Eltantawy, Fotouh Rashed Mansour, Amina M. Salama Pathogens and Global Health.2024; 118(1): 47. CrossRef
Neurobehavioral Disorders and Pathological Changes in the Brain of Mice Are Caused by Chronic Toxocara canis Larval Invasion with Low to Moderate Inoculum Nicol Bernardová, Jan Novák, Petr Horák, Chia-Kwung Fan, Libuše Kolářová Acta Parasitologica.2024; 69(4): 1736. CrossRef
Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice Amina M. Salama, Rasha A. Elmahy, Hoda A. Ibrahim, Alaa Ibrahim Mohamed Amer, Asmaa Fawzy Eltantawy, Dina I. Elgendy Parasitology Research.2023; 122(12): 3213. CrossRef
Cyclosporine A increases the intensity of Toxocara canis infection in swiss mice W. D. S. Terto, M. Q. de Moura, J. L. Borchardt, F. D. S. Santos, L. F. da Costa Avila, N. B. Pinheiro, F. P. Leivas Leite, M. M. Villela, M. E. A. Berne Brazilian Journal of Biology.2022;[Epub] CrossRef
Glial Fibrillary Acidic Protein and Ionized Calcium-Binding Adapter Molecule 1 Immunostaining Score for the Central Nervous System of Horses With Non-suppurative Encephalitis and Encephalopathies Gisele Silva Boos, Klaus Failing, Edson Moleta Colodel, David Driemeier, Márcio Botelho de Castro, Daniele Mariath Bassuino, José Diomedes Barbosa, Christiane Herden Frontiers in Veterinary Science.2021;[Epub] CrossRef
Diallyl sulfide alleviates cyclophosphamide-induced nephropathic encephalopathy in rats Shereen M. Galal, Heba H. Mansour, Abeer A. Elkhoely Toxicology Mechanisms and Methods.2020; 30(3): 208. CrossRef
Mesenchymal stem cells combined with albendazole as a novel therapeutic approach for experimental neurotoxocariasis E. V. N. Beshay, S. A. El-Refai, G. S. Sadek, A. A. Elbadry, F. H. Shalan, A. F. Afifi Parasitology.2020; 147(7): 799. CrossRef
Histopathological characterization of Toxocara canis- and T. cati-induced neurotoxocarosis in the mouse model Andrea Springer, Lea Heuer, Elisabeth Janecek-Erfurth, Andreas Beineke, Christina Strube Parasitology Research.2019; 118(9): 2591. CrossRef
Developmental stages and viability of Toxocara canis eggs outside the host Iman Fathy Abou-El-Naga Biomédica.2018; 38(2): 189. CrossRef
Seroprevalence and Risk Factors for Toxocara canis Infection in Serbia During 2015 Simona Gabrielli, Suzana Tasić-Otašević, Aleksandra Ignjatović, Maurizio Fraulo, Marija Trenkić-Božinović, Stefan Momčilović, Gabriella Cancrini Foodborne Pathogens and Disease.2017; 14(1): 43. CrossRef
Rosan Barbosa de Matos, Suzana Braga-de-Souza, Bruno Pena Seara Pitanga, Victor Di?genes Amaral da Silva, Erica Etelvina Viana de Jesus, Alexandre Morales Pinheiro, Maria de F?tima Dias Costa, Ramon dos Santos El-Bacha, C?tia Suse de Oliveira Ribeiro, Silvia Lima Costa
Korean J Parasitol 2014;52(6):613-619. Published online December 23, 2014
Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation.
Citations
Citations to this article as recorded by
A Dietary Plant Extract Formulation Helps Reduce Flea Populations in Cats: A Double-Blind Randomized Study Damien Banuls, Jessie Brun, Jean-Louis Blua, Marie Christine Cadiergues Pharmaceuticals.2023; 16(2): 195. CrossRef
Nitric Oxide Production in mixed cultures of infected rats with Neospora caninum and treated with Jataí Honey (Tetragonisca angustula) Ângela Cristina de Oliveira Lima, Luciana dos Santos Freitas, Carlos Alfredo Lopes De Carvalho, Alexandre Moraes Pinheiro Archives of Health.2023; 4(1): 166. CrossRef
The immunomodulatory activity of Chenopodium ambrosioides reduces the parasite burden and hepatic granulomatous inflammation in Schistosoma mansoni-infection João Gustavo Mendes Rodrigues, Paula Sibelly Veras Albuquerque, Johnny R Nascimento, Jaianna Andressa Viana Campos, Andressa S S Godinho, Sulayne Janayna Araújo, Jefferson Mesquita Brito, Caroline M Jesus, Guilherme Silva Miranda, Michelle C Rezende, Debo Journal of Ethnopharmacology.2021; 264: 113287. CrossRef
Anti-helminthic activity of Momordica charantia L. against Fasciola hepatica eggs after twelve days of incubation in vitro Cíntia A.J. Pereira, Laura L.S. Oliveira, Aytube L. Coaglio, Fernanda S.O. Santos, Rodolfo S.M. Cezar, Tiago Mendes, Fernando L.P. Oliveira, Gustavo Conzensa, Walter S. Lima Veterinary Parasitology.2016; 228: 160. CrossRef
Docking studies of flavonoid compounds as inhibitors of β-ketoacyl acyl carrier protein synthase I (Kas I) of Escherichia coli Ghalia Sabbagh, Noura Berakdar Journal of Molecular Graphics and Modelling.2015; 61: 214. CrossRef
Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-α, IL-6, and IL-1β, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.
Citations
Citations to this article as recorded by
Providing an in vitro depiction of microglial cells challenged with immunostimulatory extracellular vesicles of Naegleria fowleri Lissette Retana Moreira, Alberto Cornet-Gomez, M. Rosario Sepulveda, Silvia Molina-Castro, Johan Alvarado-Ocampo, Frida Chaves Monge, Mariana Jara Rojas, Antonio Osuna, Elizabeth Abrahams Sandí Frontiers in Microbiology.2024;[Epub] CrossRef
Transcriptomic profiling of “brain-eating amoeba” Naegleria fowleri infection in mice: the host and the protozoa perspectives Vincent Guerlais, Nina Allouch, E. Ashley Moseman, Alicja W. Wojciechowska, Jakub W. Wojciechowski, Isabel Marcelino Frontiers in Cellular and Infection Microbiology.2024;[Epub] CrossRef
Pro-inflammatory cytokine responses to Naegleria fowleri infection Ching-wen Chen, E. Ashley Moseman Frontiers in Tropical Diseases.2023;[Epub] CrossRef
Naegleria fowleri Extracellular Vesicles Induce Proinflammatory Immune Responses in BV-2 Microglial Cells Hương Giang Lê, Jung-Mi Kang, Tuấn Cường Võ, Won Gi Yoo, Byoung-Kuk Na International Journal of Molecular Sciences.2023; 24(17): 13623. CrossRef
Three encephalitis-causing amoebae and their distinct interactions with the host Maarten J. Sarink, Nadia L. van der Meijs, Kristin Denzer, Leo Koenderman, Aloysius G.M. Tielens, Jaap J. van Hellemond Trends in Parasitology.2022; 38(3): 230. CrossRef
Naegleria fowleri Cathepsin B Induces a Pro-Inflammatory Immune Response in BV-2 Microglial Cells via NF-κB and AP-1 Dependent-MAPK Signaling Pathway Hương Giang Lê, Jung-Mi Kang, Tuấn Cường Võ, Byoung-Kuk Na International Journal of Molecular Sciences.2022; 23(15): 8388. CrossRef
Parasite infections, neuroinflammation, and potential contributions of gut microbiota Jérémy Alloo, Ines Leleu, Corinne Grangette, Sylviane Pied Frontiers in Immunology.2022;[Epub] CrossRef
Fowlerstefin, a cysteine protease inhibitor of Naegleria fowleri, induces inflammatory responses in BV-2 microglial cells in vitro Thị Lam Thái, Jung-Mi Kang, Hương Giang Lê, Jinyoung Lee, Won Gi Yoo, Ho-Joon Shin, Woon-Mok Sohn, Byoung-Kuk Na Parasites & Vectors.2020;[Epub] CrossRef
Toll-like receptors participate in Naegleria fowleri recognition Moisés Martínez-Castillo, Leopoldo Santos-Argumedo, José Manuel Galván-Moroyoqui, Jesús Serrano-Luna, Mineko Shibayama Parasitology Research.2018; 117(1): 75. CrossRef
Morphological and functional changes of microglia cultured under different oxygen concentrations and the analysis of related mechanisms Xing Wu, Tengbo Yu, Hongyan Xu, Xiuming Sun, Dewei Kou, Liping Li Experimental and Therapeutic Medicine.2017;[Epub] CrossRef
Biology and pathogenesis of Naegleria fowleri Ruqaiyyah Siddiqui, Ibne Karim M. Ali, Jennifer R. Cope, Naveed Ahmed Khan Acta Tropica.2016; 164: 375. CrossRef
NLRP3 Inflammasome Activation in THP-1 Target Cells Triggered by Pathogenic Naegleria fowleri Jong-Hyun Kim, Hae-Jin Sohn, Jong-Kyun Yoo, Heekyoung Kang, Gi-Sang Seong, Yong-Joon Chwae, Kyongmin Kim, Sun Park, Ho-Joon Shin, J. A. Appleton Infection and Immunity.2016; 84(9): 2422. CrossRef
Novel cathepsin B and cathepsin B-like cysteine protease of Naegleria fowleri excretory–secretory proteins and their biochemical properties Jinyoung Lee, Jong-Hyun Kim, Hae-Jin Sohn, Hee-Jong Yang, Byoung-Kuk Na, Yong-Joon Chwae, Sun Park, Kyongmin Kim, Ho-Joon Shin Parasitology Research.2014; 113(8): 2765. CrossRef
Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increasse of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.
Citations
Citations to this article as recorded by
Cloning of nf-profilin and intercellular interaction with nf-actin in Naegleria fowleri cysts Hae-Jin Sohn, A-Jeong Ham, A-Young Park, Jeong-Heon Lee, Sun Park, Ho-Joon Shin, Jong-Hyun Kim Scientific Reports.2025;[Epub] CrossRef
Advances in the study of extracellular vesicles of Naegleria fowleri and their role in contact-independent pathogenic mechanisms Ismael Castelan-Ramírez, Catalina Flores-Maldonado, Dolores Hernández-Martínez, Lizbeth Salazar-Villatoro, Alberto Daniel Saucedo-Campos, David Segura-Cobos, Adolfo René Méndez-Cruz, Maritza Omaña-Molina Parasites & Vectors.2025;[Epub] CrossRef
A comprehensive review on the neurological impact of parasitic infections Firooz Shahrivar, Ata Moghimi, Ramin Hosseinzadeh, Mohammad Hasan Kohansal, Ali Mortazavi, Tahereh Mikaeili Galeh, Ehsan Ahmadpour Microbial Pathogenesis.2025; 206: 107762. CrossRef
Molecular mechanisms and therapeutic strategies of Naegleria fowleri Carter (1970): a review of the fatal brain-eating amoeba N. Datta The Journal of V. N. Karazin Kharkiv National University, Series "Biology".2024; (42): 22. CrossRef
Differential Exoproteome and Biochemical Characterisation of Neoparamoeba perurans Kerrie Ní Dhufaigh, Natasha Botwright, Eugene Dillon, Ian O’Connor, Eugene MacCarthy, Orla Slattery Microorganisms.2021; 9(6): 1258. CrossRef
Naegleria fowleri Induces Jurkat T Cell Death via O-deGlcNAcylation Young Ah Lee, Kyeong Ah Kim, Myeong Heon Shin The Korean Journal of Parasitology.2021; 59(5): 501. CrossRef
Fowlerstefin, a cysteine protease inhibitor of Naegleria fowleri, induces inflammatory responses in BV-2 microglial cells in vitro Thị Lam Thái, Jung-Mi Kang, Hương Giang Lê, Jinyoung Lee, Won Gi Yoo, Ho-Joon Shin, Woon-Mok Sohn, Byoung-Kuk Na Parasites & Vectors.2020;[Epub] CrossRef
Cellular characterization of actin gene concerned with contact‐dependent mechanisms in Naegleria fowleri Hae‐Jin Sohn, Kyoung‐Ju Song, Heekyoung Kang, A‐Jeong Ham, Jae‐Ho Lee, Yong‐Joon Chwae, Kyongmin Kim, Sun Park, Jong‐Hyun Kim, Ho‐Joon Shin Parasite Immunology.2019;[Epub] CrossRef
Cytopathic Change and Inflammatory Response of Human Corneal Epithelial Cells Induced by Acanthamoeba castellanii Trophozoites and Cysts Hae-Jin Sohn, Ga-Eun Seo, Jae-Ho Lee, A-Jeong Ham, Young-Hwan Oh, Heekyoung Kang, Ho-Joon Shin The Korean Journal of Parasitology.2019; 57(3): 217. CrossRef
In Vitro Activity of Statins against Naegleria fowleri Aitor Rizo-Liendo, Ines Sifaoui, María Reyes-Batlle, Olfa Chiboub, Rubén L. Rodríguez-Expósito, Carlos J. Bethencourt-Estrella, Desirée San Nicolás-Hernández, Edyta B. Hendiger, Atteneri López-Arencibia, Pedro Rocha-Cabrera, José E. Piñero, Jacob Lorenzo- Pathogens.2019; 8(3): 122. CrossRef
Excretory and Secretory Proteins of Naegleria fowleri Induce Inflammatory Responses in BV‐2 Microglial Cells Jinyoung Lee, Jung‐Mi Kang, Tae Im Kim, Jong‐Hyun Kim, Hae‐Jin Sohn, Byoung‐Kuk Na, Ho‐Joon Shin Journal of Eukaryotic Microbiology.2017; 64(2): 183. CrossRef
Amphotericin B induces apoptosis-like programmed cell death in Naegleria fowleri and Naegleria gruberi Roberto Cárdenas-Zúñiga, Angélica Silva-Olivares, José D' Artagnan Villalba-Magdaleno, Virginia Sánchez-Monroy, Jesús Serrano-Luna, Mineko Shibayama Microbiology.2017; 163(7): 940. CrossRef
Production and characterization of monoclonal antibodies against cathepsin B and cathepsin B-Like proteins of Naegleria fowleri Gi-Sang Seong, Hae-Jin Sohn, Heekyoung Kang, Ga-Eun Seo, Jong-Hyun Kim, Ho-Joon Shin Experimental Parasitology.2017; 183: 171. CrossRef
Biology and pathogenesis of Naegleria fowleri Ruqaiyyah Siddiqui, Ibne Karim M. Ali, Jennifer R. Cope, Naveed Ahmed Khan Acta Tropica.2016; 164: 375. CrossRef
Naegleria fowleri after 50 years: is it a neglected pathogen? Moisés Martínez-Castillo, Roberto Cárdenas-Zúñiga, Daniel Coronado-Velázquez, Anjan Debnath, Jesús Serrano-Luna, Mineko Shibayama Journal of Medical Microbiology.2016; 65(9): 885. CrossRef
NLRP3 Inflammasome Activation in THP-1 Target Cells Triggered by Pathogenic Naegleria fowleri Jong-Hyun Kim, Hae-Jin Sohn, Jong-Kyun Yoo, Heekyoung Kang, Gi-Sang Seong, Yong-Joon Chwae, Kyongmin Kim, Sun Park, Ho-Joon Shin, J. A. Appleton Infection and Immunity.2016; 84(9): 2422. CrossRef
Novel cathepsin B and cathepsin B-like cysteine protease of Naegleria fowleri excretory–secretory proteins and their biochemical properties Jinyoung Lee, Jong-Hyun Kim, Hae-Jin Sohn, Hee-Jong Yang, Byoung-Kuk Na, Yong-Joon Chwae, Sun Park, Kyongmin Kim, Ho-Joon Shin Parasitology Research.2014; 113(8): 2765. CrossRef
Naegleria fowleriLysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells Yang-Jin Lee, Chang-Eun Park, Jong-Hyun Kim, Hae-Jin Sohn, Jinyoung Lee, Suk-Yul Jung, Ho-Joon Shin The Korean Journal of Parasitology.2011; 49(3): 285. CrossRef
Screening of Swiss hot spring resorts for potentially pathogenic free-living amoebae Christian Gianinazzi, Marc Schild, Beatrice Zumkehr, Fritz Wüthrich, Irina Nüesch, Regula Ryter, Nadia Schürch, Bruno Gottstein, Norbert Müller Experimental Parasitology.2010; 126(1): 45. CrossRef
Immunodominant antigens in Naegleria fowleri excretory–secretory proteins were potential pathogenic factors Jong-Hyun Kim, Ae-Hee Yang, Hae-Jin Sohn, Daesik Kim, Kyoung-Ju Song, Ho-Joon Shin Parasitology Research.2009; 105(6): 1675. CrossRef
First
Prev
