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PLoS Neglected Tropical Diseases May 2024Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in...
Inflammatory and immunopathological differences in brains of permissive and non-permissive hosts with Angiostrongylus cantonensis infection can be identified using 18F/FDG/PET-imaging.
BACKGROUND
Angiostrongylus cantonensis is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. 18F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that A. cantonensis infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using in vivo 18F-FDG PET imaging.
METHODOLOGY/FINDINGS
Non-permissive host ICR mice and permissive host SD rats were infected with A. cantonensis, and the effects of the resulting inflammation on 18F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of 18F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-γ and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that 18F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain.
CONCLUSIONS
An in vivo 18F-FDG/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of A. cantonensis-infected mice and rats.
PubMed: 38805557
DOI: 10.1371/journal.pntd.0012188 -
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 -
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 -
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