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Tropical Medicine and Infectious Disease May 2024The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching....
The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in -infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.
PubMed: 38787044
DOI: 10.3390/tropicalmed9050111 -
Acta Tropica Aug 2024Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine...
Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2-3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.
Topics: Animals; Angiostrongylus cantonensis; Kynurenine; Strongylida Infections; Mice, Inbred BALB C; Meningitis; Blood-Brain Barrier; Tryptophan; Mice; Dexamethasone; Indoleamine-Pyrrole 2,3,-Dioxygenase; Tandem Mass Spectrometry; Chromatography, Liquid; Male; Disease Models, Animal; Eosinophilia; Immunohistochemistry; Metabolic Networks and Pathways; Female; Blotting, Western
PubMed: 38763319
DOI: 10.1016/j.actatropica.2024.107251 -
Parasitology Research May 2024The metastrongyloid nematode Angiostrongylus cantonensis causes eosinophilic meningitis in a variety of homeothermic hosts including humans. Third-stage infectious...
The metastrongyloid nematode Angiostrongylus cantonensis causes eosinophilic meningitis in a variety of homeothermic hosts including humans. Third-stage infectious larvae develop in gastropods as intermediate hosts. Humans are usually infected by intentional or incidental ingestion of an infected mollusk or paratenic host (poikilothermic vertebrates and invertebrates). The infection may also hypothetically occur through ingestion of food or water contaminated by third-stage larvae spontaneously released from gastropods. Larvae are thought to be released in greater numbers from the intermediate host exposed to stress. This study aimed to compare larval release from stressed with unstressed gastropods. Experimentally infected Limax maximus and Lissachatina fulica were exposed to a stress stimulus (shaking on an orbital shaker). The mucus was collected before and after the stress and examined microscopically and by qPCR for the presence of A. cantonensis larvae and their DNA. In the case of L. maximus, no larvae were detected microscopically in the mucus, but qPCR analysis confirmed the presence of A. cantonensis DNA in all experimental replicates, without clear differences between stressed and non-stressed individuals. In contrast, individual larvae of A. cantonensis were found in mucus from Li. fulica after stress exposure, which also reflects an increased number of DNA-positive mucus samples after stress. Stress stimuli of intensity similar to the transport or handling of mollusks can stimulate the release of larvae from highly infected intermediate hosts. However, these larvae are released in small numbers. The exact number of larvae required to trigger neuroangiostrongyliasis is unknown. Therefore, caution is essential when interacting with potential intermediate hosts in regions where A. cantonensis is endemic.
Topics: Animals; Angiostrongylus cantonensis; Larva; Stress, Physiological; Gastropoda; Strongylida Infections; Mucus; Real-Time Polymerase Chain Reaction
PubMed: 38755287
DOI: 10.1007/s00436-024-08232-y -
Parasites & Vectors May 2024Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling...
BACKGROUND
Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified.
METHODS
In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR).
RESULTS
The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed.
CONCLUSIONS
This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.
Topics: Animals; RNA, Long Noncoding; Angiostrongylus cantonensis; Strongylida Infections; Brain; Mice; Mice, Inbred BALB C; Larva; MicroRNAs; Gene Expression Profiling; Female; RNA, Messenger
PubMed: 38715092
DOI: 10.1186/s13071-024-06278-6 -
Helminthologia Mar 2024The continuous challenges of land use change have brought potential threats to biodiversity and the spread of zoonotic diseases. In this study, synanthropic rodents and...
The continuous challenges of land use change have brought potential threats to biodiversity and the spread of zoonotic diseases. In this study, synanthropic rodents and their helminth parasites were used as sentinels to assess the potential impact of land use on zoonosis. Rats were collected in different ecosystems, namely agricultural, agroforest, and residential areas in the northeastern sub-watersheds of Mount Makiling, Laguna, Philippines. Three (3) species of rats were captured, namely, and . Of the total 180 rats collected, 92.7 % were found infected with helminth parasites, namely and (cestodes); , , and sp. (nematodes); and (trematode). Of these 11 species, nine (9) were considered zoonotic. This study provides important information on the helminth parasites of rats in the northeastern sub-watersheds of Mount Makiling and the potential threat of zoonotic transmission due to increasing land use change and urbanization in the area. Moreover, urbanization can provide favorable eco-epidemiological conditions for rodent-borne pathogens, such as parasites, that are seriously threatening agricultural settings and human settlements in these areas.
PubMed: 38659471
DOI: 10.2478/helm-2024-0005 -
Parasites & Vectors Apr 2024Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological...
BACKGROUND
Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical.
METHODS
We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration.
RESULTS
Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex.
CONCLUSIONS
Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.
Topics: Animals; Female; Male; Mice; Angiostrongylus cantonensis; Brain; Energy Metabolism; Hypothalamic Hormones; Melanins; Pituitary Hormones; Strongylida Infections
PubMed: 38654385
DOI: 10.1186/s13071-024-06267-9 -
Biomedical Journal Apr 2024We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.
BACKGROUND
We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.
MATERIALS AND METHODS
C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis.
RESULTS
In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system.
CONCLUSIONS
Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.
PubMed: 38636898
DOI: 10.1016/j.bj.2024.100727 -
Zoonoses and Public Health Jun 2024The rat lungworm, Angiostrongylus cantonensis, has recently been found in the city of Valencia, parasitizing rats, Rattus norvegicus and Rattus rattus, its natural...
AIM
The rat lungworm, Angiostrongylus cantonensis, has recently been found in the city of Valencia, parasitizing rats, Rattus norvegicus and Rattus rattus, its natural definitive hosts. This is the first finding of this zoonotic nematode in continental Europe. After informing local and national health authorities, the collection of local terrestrial snails took place with the aim of elucidating their potential role as intermediate hosts of A. cantonensis.
METHODS AND RESULTS
A total of 145 terrestrial snails, belonging to the species Cernuella virgata, Cornu aspersum, Eobania vermiculata, Otala punctata, Pseudotachea splendida, Rumina decollata and Theba pisana, were randomly collected between May and December 2022 in public gardens, parks and orchards in six districts of Valencia, in five of which A. cantonensis had been reported previously in rats. Once collected and identified, the snails were frozen at -20°C. Subsequently, the DNA was isolated and screened by PCR using specific primers targeting the A. cantonensis COI gene. Seven individual snails, belonging to the species C. virgata, C. aspersum and T. pisana, were positive, for an overall prevalence of 4.8%. The PCR product from one of them was sequenced by Sanger sequencing.
CONCLUSIONS
The three positive terrestrial snail species are among the edible species that are frequently included in various dishes in Spain. C. virgata is reported as a previously unrecorded intermediate host and should be added to the list of more than 200 species of terrestrial snails that have been reported worldwide as intermediate hosts of the rat lungworm. Considering that these terrestrial snails may release infective larvae of A. cantonensis on leafy green vegetables on which they feed and during their handling and preparation for consumption, prophylactic measures to prevent human neuroangiostrongyliasis in Valencia and other regions to which this zoonotic parasite may spread are recommended.
Topics: Animals; Angiostrongylus cantonensis; Snails; Spain; Zoonoses; Strongylida Infections; Rats; Humans
PubMed: 38553828
DOI: 10.1111/zph.13131 -
Travel Medicine and Infectious Disease 2024
Topics: Humans; Colombia; Animals; Strongylida Infections; Angiostrongylus; Intestinal Perforation; Male; Female
PubMed: 38537928
DOI: 10.1016/j.tmaid.2024.102706 -
Pathogens (Basel, Switzerland) Mar 2024Metastrongyloidea includes nematodes that parasitize mammals, mainly infecting their respiratory and cardiovascular systems, and are responsible for emerging zoonosis in...
Metastrongyloidea includes nematodes that parasitize mammals, mainly infecting their respiratory and cardiovascular systems, and are responsible for emerging zoonosis in the world. Terrestrial mollusks are their main intermediate hosts, with few exceptions. Here we present the results of a malacological survey to know the distribution of in Macapá, Amapá, in the Brazilian Amazon region, after the report of a case of eosinophilic meningitis in 2018. Mollusks were collected in 45 neighborhoods between March 2019 and February 2020. They were identified, parasitologically analyzed, and their nematodes parasites were identified based on the morphology and MT-CO1 sequencing. Infections of An. cantonensis were observed in , and . These are the first records of the natural infection of the last two species by in the Brazilian Amazon region. The angiostrongylid , which parasitizes cats, was also detected parasitizing and . This is also the first record of the slug infected by . The highest infection rates were recorded in neighborhoods where the environment conditions favor the proliferation of both mollusks and rodents. The results demonstrate the ample distribution of in Macapá and the need for surveillance and mollusk vector control in Brazil and other countries.
PubMed: 38535598
DOI: 10.3390/pathogens13030255