Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

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.

Parasitism in Rattus rattus and sympatric Achatina fulica by Angiostrongylus cantonensis in an urban park in southeast Brazil.

In this study, rodents (Rattus rattus) and mollusks (Achatina fulica) were captured in a small forest located in a large metropolitan city in Brazil, and they were examined to investigate possible parasitism by Angiostrongylus cantonensis. The parasites were recovered as helminths from the pulmonary arteries of the synanthropic rodents and as third-stage larvae (with Metastrongylidae family characteristics) from the mollusks. To confirm the species, these larvae were used to experimentally infect Rattus norvegicus for the posterior recovery of adult helminths. To identify the adult helminths, morphological, morphometric, molecular, and phylogenetic techniques were employed. Furthermore, we also characterized the histological lesions associated with parasitism in naturally infected definitive hosts. Our results demonstrated the occurrence of a natural life cycle of A. cantonensis (with the presence of adult helminths) in definitive hosts, Rattus rattus, and third-stage larvae in an intermediate host, A. fulica. In free-living rodents, lesions of granulomatous pneumonia in the lungs and meningitis in the brain were also found. These results warn of the risk of accidental transmission of A. cantonensis to human residents around the park because of the extensive interaction among the fauna of the park, domestic animals, and the surrounding human population.

Reproductive alterations of Biomphalaria glabrata (Say, 1818) infected with Angiostrongylus cantonensis (Chen, 1935) and exposed to Euphorbia milii var. hislopii latex.

The natural phytochemical latex of Euphorbia milii var. hislopii is one of the most promising natural molluscicides for the control of Biomphalaria glabrata, and has been widely studied under laboratory conditions for selective control of schistosomiasis transmission. However, the effect of this product on B. glabrata infected by other helminths had not yet been investigated. The present study reports evaluation of the effect of E. milii var. hislopii latex on the survival and reproductive activity of B. glabrata infected by Angiostrongylus cantonensis. For this purpose, the following groups were formed: control (C), exposed (E), infected (I) and infected and exposed for different time intervals (1 day - I+E-1D, 7 days - I+E-7D, 14 days - I+E-14D, 21 days - I+E-21D and 28 days - I+E-28D). The experimental infection was performed with L1 larvae of A. cantonensis and exposure to 0.08 mg/L (LC50) of E. milii latex for a period of 24 hours. We analyzed the effects of E. milii latex on the survival of snails during four weeks, reproductive parameters and possible histophysiopathological changes in the gonad and albumen gland of the snails. Regarding survival, there was reduction of more than 50% in the groups exposed to latex (E and I + E) compared to the control group. As for the number of ovigerous masses, eggs, and average number of hatched snails, significant increases were observed in the I+E-1D group at the 4th week compared to the control group and the other weeks in the same group. Angiostrongylus cantonensis larvae were observed in the gonad and albumen gland from day 21 and 28 of infection in groups I and I+E, respectively, with granuloma-like formation. At these observation periods and in these groups, an increase in galactogen was observed in the albumen gland, which influenced egg laying, suggesting the existence of a fecundity compensation mechanism phenomenon. It was possible to conclude that both stressors - A. cantonensis infection and exposure to E. milii latex - directly influenced the survival and reproductive parameters of B. glabrata.

Case Report: Angiostrongylus cantonensis Infection Presenting as Small Fiber Neuropathy.

Angiostrongylus cantonensis is an emerging parasite that is the most common cause of eosinophilic meningitis worldwide. Human infection typically presents with headache, neck stiffness, and paresthesia. We report a case of a woman with PCR positive A. cantonensis infection who presented with symptoms of small fiber neuropathy (SFN) but no headache. SFN was confirmed by skin biopsy. After failing standard medications for neuropathy, she was treated with intravenous lidocaine with considerable improvement. However, she required medications for 1 year to treat her chronic neuropathy. Infection by A. cantonensis should be added to the list of causes of SFN, and its potential to cause chronic sequelae should be appreciated.

Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis.

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.

Detection of antigens in paraffin sections of worms and snails infected by Angiostrongylus cantonensis by immunofluorescence reaction / Detecção de antígenos em cortes parafinados de vermes e caramujos infectados por Angiostrongylus cantonensis pela reação de imunofluorescência

The Indirect Immunofluorescence Assay (IFA) was used to identify stage-specific antigenic structures in paraffin sections of female larvae and worms and snails tissues, infected with third stage larvae of Angiostrongylus cantonensis. Sera from eosinophilic meningitis cases were used to assess reactivity. Non-reactive sera from patients with other parasitic diseases and from individuals without other etiologies were used as controls for cross-reactivity. Larvae and worms showed high reactivity to IgG antibodies. IgM antibodies reacted with low intensity only to larvae. Fluorescent reactions were observed in the cuticles and internal structures on worms sections, with a marked reaction in the uterus content. In the snail tissues, the larvae were found exclusively inside the granulomas, with fluorescent markings in the cuticles of the larvae and inside the granulomatous tissues. This fluorescent pattern suggests the presence of excretory/secretory antigens distributed throughout the granulomas. Expressive cross-reactivity occurred in sera from patients with other parasitic diseases, especially strongyloidiasis. The use of IFA applied to paraffin sections to identify structures with antigenic potential and the study of new serological markers, can contribute to the improvement of the laboratory diagnosis of eosinophilic meningitis. (AU)

A Reação de Imunofluorescência Indireta (RIFI) foi utilizada para localizar antígenos em estruturas estágio-específicas em cortes parafinados de vermes fêmeas e em tecidos de caramujos do Gênero Biomphalaria infectados com larvas de terceiro estágio de Angiostrongylus cantonensis. Soros de casos confirmados de meningite eosinfílica foram usados para avaliação da reatividade. Soros não reagentes de casos suspeitos; de pacientes com outras parasitoses e de indivíduos sem outras etiologias foram utilizados como controle de reatividade cruzada. Anticorpos da classe IgG foram reativos para antígenos presentes nos dois estágios e, anticorpos IgM somente para o estágio larvário. Nos cortes de vermes, as marcações fluorescentes foram assinaladas nas cutículas e estruturas internas, com acentuada marcação para os conteúdos uterinos. Nos tecidos dos caramujos as larvas foram encontradas exclusivamente no interior dos granulomas, com marcações fluorescentes nas cutículas das larvas e no interior dos tecidos granulomatosos. O padrão de fluorescência no granuloma sugere a marcação de antígenos excretores/secretores. Reatividade cruzada mais expressiva ocorreu com anticorpos presentes em soros de pacientes com outras parasitoses, com destaque para estrongiloidíase. A RIFI em cortes parafinados abre novas perspectivas para identificação de antígenos e de marcadores sorológicos, que possam ser aplicados no aprimoramento do diagnóstico laboratorial da meningite eosinofílica. (AU)

Heme oxygenase-1 modulates brain inflammation and apoptosis in mice with angiostrongyliasis.

The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or meningoencephalitis. Heme oxygenase 1 (HO-1) has several cytoprotective properties such as anti-oxidative, anti-inflammatory, and anti-apoptotic effects. HO-1 in brain tissues was induced in A. cantonensis-infected group and showed positive modulation in cobalt protoporphyrin (CoPP)-treated groups. Assay methods for the therapeutic effect include western blot analysis, enzyme-linked immunosorbent assay, gelatin zymography, blood-brain barrier permeability evaluation and eosinophil count in cerebrospinal fluid. The combination of albendazole (ABZ) and CoPP significantly decreased pro-inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1ß, IL-5, and IL-33 but significantly increased anti-inflammatory cytokines IL-10 and transforming growth factor-ß. In addition, worm recovery, matrix metalloproteinase-9, BBB permeability, and eosinophil counts were decreased in the ABZ and CoPP co-treated groups. Induction of HO-1 with CoPP strongly inhibited the protein levels of caspase-3 and increased the induction of annexin-V and B-cell leukemia 2. Thus, co-treatment with ABZ and CoPP prevented A. cantonensis-induced eosinophilic meningoencephalitis and its anti-apoptotic effect by promoting HO-1 signaling prior to BBB dysfunction. HO-1 induction might be a therapeutic modality for eosinophilic meningoencephalitis.

Angiostrongylus cantonensis en Achatina fulica en la provincia del Napo, Ecuador y el riesgo incrementado de angiostrongiliasis / Angiostrongylus cantonensis in Achatina fulica in Napo province, Ecuador and the increased risk of angiostrongyliasis

Introducción: Angiostrongylus cantonensis es reconocido como uno de los principales patógenos causantes de la meningoencefalitis eosinofílica, fue identificado en Ecuador por primera vez en 2008. Métodos: se recolectaron 1476 ejemplares de Achatina fulica con el método de captura por unidad de esfuerzo durante 30 minutos, en 3 cantones de la provincia del Napo, con el fin de establecer la prevalencia de infección por A. cantonensis Resultados: el porcentaje total de caracoles infectados fue de 46,5% (687/1476). Conclusiones: Los resultados revelan una amplia distribución de A. fulica infectado con A. cantonensis, lo que, sumado a la gran cantidad de hospederos definitivos presentes, indica que un número considerable de personas tiene riesgo de adquirir angiostrongiliasis. Se necesita intervenciones educativas comunitaria orientadas a formación sanitaria, recalcando el riesgo de adquirir la infección parasitaria, principalmente por el consumo de A. fulica, crudos y/o con cocción inadecuada, principal forma de contagio. Además, se recomienda vigilancia rigurosa y control de los hospedadores involucrados, saneamiento ambiental, haciendo insistencia en factores relacionados con los hábitos biológico del caracol gigante africano, entre ello alimentos (vegetales), suelos y derivados del caracol de uso artesanal; para prevenir la aparición de casos esporádicos y de brotes de la enfermedad(AU)

Introduction: Angiostrongylus cantonensis is recognized as one of the main pathogens that cause eosinophilic meningoencephalitis, it was identified in Ecuador for the first time in 2008. Methods: 1476 specimens of Achatina fulica were collected using the capture method per unit of effort for 30 minutes, in 3 cantons of the Napo province, in order to establish the prevalence of infection by A. cantonensis Results: the total percentage of infected snails was 46.5% (687/1476). Conclusions: The results reveal a wide distribution of A. fulica infected with A. cantonensis, which, added to the large number of definitive hosts present, indicates that a considerable number of people are at risk of acquiring angiostrongyliasis. Community educational interventions aimed at health training are needed, emphasizing the risk of acquiring parasitic infection, mainly due to the consumption of A. fulica, raw and/or inadequately cooked, the main form of contagion. In addition, rigorous surveillance and control of the hosts involved, environmental sanitation, insisting on factors related to the biological habits of the giant African snail, including food (vegetables), soil and snail derivatives for artisanal use; to prevent the appearance of sporadic cases and outbreaks of the disease(AU)

First Case of Subretinal Ocular Angiostrongyliasis Associated with Retinal Detachment in the United States.

Angiostrongylus cantonensis, commonly known as the rat lungworm, is mostly found in Asia, the Pacific Basin, and the Caribbean, but is also endemic in Hawai'i, especially on the Island of Hawai'i. Ocular angiostrongyliasis is an uncommon but previously reported complication associated with permanent vision loss. This is the first reported case of ocular angiostrongyliasis involving the retina or posterior segment of the eye in the US. A 24-year-old male from Chicago visited the Island of Hawai'i, where he worked on a farm and ate a vegetarian diet. When he returned to Chicago, he became sick and was hospitalized for eosinophilic meningitis. One month later, he developed a retinal detachment which required surgical repair involving a pars plana vitrectomy. During the reattachment of the retina during surgery, a live motile was identified nematode in the subretinal space. An endolaser probe immobilized and killed the nematode, and it was subsequently extracted through the sclerotomy. Thermal scars around all retinal holes including the retinotomy site were made to stabilize the retina, and perfluoropropane gas was injected to achieve temporary tamponade. Thereafter, the patient's cerebrospinal fluid returned positive for angiostrongylus cantonensis antibodies. During extended follow-up, the patient eventually lost all vision in the affected eye due to recurrent retinal detachment. This case of ocular angiostrongyliasis demonstrates the importance of obtaining travel history from endemic areas, knowing the risk of developing eosinophilic meningitis, and understanding the risk of permanent vision loss in cases involving the retina.

Exosome-Depleted Excretory-Secretory Products of the Fourth-Stage Larval Angiostrongylus cantonensis Promotes Alternative Activation of Macrophages Through Metabolic Reprogramming by the PI3K-Akt Pathway.

Angiostrongylus cantonensis (AC), which parasitizes in the brain of the non-permissive host, such as mouse and human, is an etiologic agent of eosinophilic meningitis. Excretory-secretory (ES) products play an important role in the interaction between parasites and hosts' immune responses. Inflammatory macrophages are responsible for eosinophilic meningitis induced by AC, and the soluble antigens of Angiostrongylus cantonensis fourth stage larva (AC L4), a mimic of dead AC L4, aggravate eosinophilic meningitis in AC-infected mice model via promoting alternative activation of macrophages. In this study, we investigated the key molecules in the ES products of AC L4 on macrophages and observed the relationship between metabolic reprogramming and the PI3K-Akt pathway. First, a co-culture system of macrophage and AC L4 was established to define the role of AC L4 ES products on macrophage polarization. Then, AC L4 exosome and exosome-depleted excretory-secretory products (exofree) were separated from AC L4 ES products using differential centrifugation, and their distinct roles on macrophage polarization were confirmed using qPCR and ELISA experiments. Moreover, AC L4 exofree induced alternative activation of macrophages, which is partially associated with metabolic reprogramming by the PI3K-Akt pathway. Next, lectin blot and deglycosylation assay were done, suggesting the key role of N-linked glycoproteins in exofree. Then, glycoproteomic analysis of exofree and RNA-seq analysis of exofree-treated macrophage were performed. Bi-layer PPI network analysis based on these results identified macrophage-related protein Hexa as a key molecule in inducing alternative activation of macrophages. Our results indicate a great value for research of helminth-derived immunoregulatory molecules, which might contribute to drug development for immune-related diseases.

Gross, microscopic, radiologic, echocardiographic and haematological findings in rats experimentally infected with Angiostrongylus cantonensis.

Although the gross and microscopic pathology in rats infected with Angiostrongylus cantonensis has been well described, corresponding changes detected using diagnostic imaging modalities have not been reported. This work describes the cardiopulmonary changes in mature Wistar rats chronically infected with moderate burdens of A. cantonensis using radiology, computed tomography (CT), CT angiography, echocardiography, necropsy and histological examinations. Haematology and coagulation studies were also performed. Thoracic radiography, CT and CT angiography showed moderately severe alveolar pulmonary patterns mainly affecting caudal portions of the caudal lung lobes and associated dilatation of the caudal lobar pulmonary arteries. Presumptive worm profiles could be detected using echocardiography, with worms seen in the right ventricular outflow tract or straddling either the pulmonary and/or the tricuspid valves. Extensive, multifocal, coalescing dark areas and multiple pale foci affecting the caudal lung lobes were observed at necropsy. Histologically, these were composed of numerous large, confluent granulomas and fibrotic nodules. Adult worms were found predominantly in the mid- to distal pulmonary arteries. An inflammatory leukogram, hyperproteinaemia and hyperfibrinogenaemia were found in most rats. These findings provide a comparative model for A. cantonensis in its accidental hosts, such as humans and dogs. In addition, the pathological and imaging changes are comparable to those seen in dogs infected with Angiostrongylus vasorum, suggesting rats infected with A. cantonensis could be a model for dogs with A. vasorum infection.

Mitochondrial dynamics in Angiostrongylus cantonensis-infected mouse brain.

Angiostrongylus cantonensis is one of the most widespread parasites causing central nervous system (CNS) diseases in mammals. Since the mitochondrion is an essential cell organelle responsible for both physiological and pathological processes, its dysfunction might lead to inflammation and multiple disorders. In this study we aimed to investigate the changes in mitochondrial dynamics that occur in the mouse brain upon infection with A. cantonensis, using molecular biology techniques such as polymerase chain reaction (PCR), western blot analysis, transmission electron microscopy (TEM), and different staining methods. Here, we show that mouse brain infected with A. cantonensis exhibits altered mitochondrial dynamics, including fission, fusion, and biogenesis. Additionally, we demonstrate that caspases and B-cell lymphoma 2 (BCL-2) were significantly upregulated in A. cantonensis-infected brain. These results are indicative of the occurrence of apoptosis during A. cantonensis infection, which was further confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. These findings suggest the change in mitochondrial dynamics in A. cantonensis-infected brain, providing another point of view on the pathogenesis of meningoencephalitis caused by A. cantonensis infection.

Immunomodulatory action of excretory-secretory products of Angiostrongylus cantonensis in a mouse tumour model.

Excretory-secretory products (ESPs) of parasitic helminths are well known to exert immunostimulation and immunomodulation in hosts. Immune regulation plays a key role in anti-tumour therapy. The present study explored the anti-tumour effect of ESPs released by Angiostrongylus cantonensis. In Hepa1-6 mouse tumour models, ESPs significantly reduced tumour growth. Tumour-bearing mice treated with ESPs had significantly higher CD3+, CD4+, and CD8+ T cell counts than those treated with Freund's adjuvant. In vitro, human hepatocarcinoma HepG2 cells, human lung cancer A549 cells, and normal human liver HL-7702 cells were co-incubated with ESPs for 24 h and 48 h. ESPs significantly accelerated HepG2 apoptosis but had no inhibitory effect on the proliferation of A549 and HL-7702 cells. Apoptotic HepG2 cells displayed condensed nuclei, apoptotic bodies, and swollen endoplasmic reticulum (ER). Expression of the endoplasmic reticulum stress (ERS)-related factors activating transcription factor 6 (ATF6) and C/EBP-homologous protein (CHOP) in HepG2 cells increased with increasing ESP concentration and treatment time. Calreticulin (CRT) is a key effector protein of ESPs, and recombinant calreticulin (rCRT) was produced in BL21 Escherichia coli (E. coli). In contrast to ESPs, rCRT markedly reduced the proliferation of HepG2 cells. The expression levels of ATF6 and CHOP in HepG2 cells treated with 30 µg/mL rCRT significantly increased at 48 h. Notably, these findings synergistically suggest that ESPs and rCRT are promising candidates for anti-tumour immunotherapy.

Lidocaine Infusion for Refractory Pain from Rat Lungworm Disease - Honolulu, Hawai'i.

Human infection with Angiostrongyloides cantonensis, or rat lungworm disease, manifests most commonly with neurologic symptoms that often include severe diffuse pain. While pain is reported by the majority of patients with rat lungworm disease, there are presently no published guidelines on the approach to pain management for these patients. Here we report a case of rat lungworm disease where severe refractory pain was the most prominent symptom and an intravenous lidocaine infusion was used as a successful treatment modality. Intravenous lidocaine has been shown to be safe and effective in neuropathic pain, refractory cancer pain, and peri-operative pain management. To our knowledge, this is the first case report on the use of lidocaine infusion for the management of refractory pain from rat lungworm disease, and among the first reports of any approach, to pain management for rat lungworm disease. We suggest that a lidocaine infusion protocol be considered when pain from rat lungworm disease fails to respond to first-line analgesics.

Particularidades de la meningoencefalitis eosinofílica en la era del caracol gigante africano / Particular features of eosinophilic meningoencephalitis in the age of the giant African snail

Introducción: la meningoencefalitis eosinofílica es una enfermedad inflamatoria infecciosa reportada en Cuba desde la década de los ochenta del siglo pasado y actualmente extendida al continente americano. Es producida por el parásito Angiostrongylus cantonensis. Objetivo: determinar si existen diferencias entre los pacientes que sufrieron meningoencefalitis eosinofílica antes y después de la introducción del caracol gigante africano. Métodos: se estudiaron un total de 19 muestras de líquido cefalorraquídeo y suero tomadas simultáneamente a cada paciente diagnosticados con meningoencefalitis eosinofílica, perteneciente a la seroraquioteca del Laboratorio Central del Líquido Cefalorraquídeo (LABCEL). Para la determinación de las proteínas albúmina e IgG se empleó como método de laboratorio la inmunodifusión radial. Resultados: el 14 por ciento de los pacientes fueron adultos antes de la aparición de este molusco, en contraste con el momento actual, donde el 50 por ciento son pacientes con edades superiores a 18 años. El porcentaje de síntesis de IgG intratecal media fue mayor en los enfermos actuales, aunque no de manera significativa. Conclusiones: . existen diferencias antes y después de la aparición del caracol gigante africano dado por la respuesta de síntesis intratecal en los pacientes asociados con el molusco que denota una mayor agresividad del parásito. La edad promedio mayor de los enfermos confirma que estos son los que más manipulan y dispersan el molusco(AU)

Introduction: eosinophilic meningoencephalitis is an infectious inflammatory disease reported in Cuba since the 1980s and currently extended to the American continent. This condition is caused by the parasite Angiostrongylus cantonensis. Objective: determine whether there are differences between the patients suffering from eosinophilic meningoencephalitis before and after the introduction of the giant African snail. Methods: a study was conducted of a total 19 cerebrospinal fluid and serum samples taken simultaneously from each of the patients diagnosed with eosinophilic meningoencephalitis and kept at the sample collection of the Central Cerebrospinal Fluid Laboratory (LABCEL). Radial immunodiffusion was the laboratory method used for determination of the proteins albumin and IgG. Results: of the patients studied, 14 percent were adults before the appearance of this mollusc, in contrast with the present moment, when 50 percent are patients aged over 18 years. The percentage of mean intrathecal synthesis of IgG was higher in the current sufferers, though not significantly. Conclusions: there are differences before and after the appearance of the giant African snail, given the intrathecal synthesis response of patients associated to the mollusc, which denotes greater aggressiveness by the parasite. The higher mean age of sufferers confirms that these are the ones who most often handle and disperse the mollusc(AU)

Angiostrongylus cantonensis activates inflammasomes in meningoencephalitic BALB/c mice.

Angiostrongylus cantonensis is a metastrongyloid nematode that causes eosinophilic meningoencephalitis in humans. A high infestation of A. cantonensis can cause permanent brain damage or even death. The inflammasome is an oligomeric molecular platform that can detect microbial pathogens and activate inflammatory cytokines. The recognition of larval surface antigens by pattern recognition receptors (PRRs) can cause oligomerization of the NOD-like receptor (NLR) or absent in melanoma 2 (AIM2) with the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) to form a caspase-1-activating scaffold. Activated caspase-1 converts pro-inflammatory cytokines into their mature, active forms. Helminths infection has been shown to activate NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasomes. In this study, we aimed to investigate the mechanism of inflammasome activation upon A. cantonensis infection in a mouse model. This study provides evidence that A. cantonensis infection can activate NLRP1B and NLRC4 inflammasomes and promote pyroptosis to cause meningoencephalitis.

Angiostrongylus cantonensis Galectin-1 interacts with Annexin A2 to impair the viability of macrophages via activating JNK pathway.

BACKGROUND: Angiostrongylus cantonensis can cause severe symptoms of central nervous system infections. In the host, this parasite localizes in the blood and cerebrospinal fluid, and its secreted components can impact immune responses. Our previous study demonstrated that immune responses were inhibited in A. cantonensis-infected mice immunized with Ac-Galectin-1 (AcGal-1). However, the mechanisms by which AcGal-1 regulates the immune responses remain unclear. Macrophages are innate immune cells that rapidly respond to infection. The direct impact of AcGal-1 on macrophages may affect the immune responses. METHODS: AcGal-1 protein was purified by nickel ion affinity chromatography. The effect of AcGal-1 on the apoptosis of macrophages was detected using CCK-8 assay, flow cytometry and western blot. Macrophage membrane proteins bound to AcGal-1 were obtained using the His-tag-based pull-down assay and identified via mass spectrometry. Co-localization of AcGal-1 and the macrophage membrane protein Annexin A2 was observed by immunofluorescence microscopy, and their interaction was validated by co-immunoprecipitation experiments. SiRNA-mediated knockdown of Annexin A2 was used to determine if AcGal-1-induced macrophage apoptosis required interaction with Annexin A2. The phosphorylation level of apoptotic signal pathway protein was detected by phospho-antibody microarray and western blot. RESULTS: Our study showed that AcGal-1 caused apoptosis of the macrophages. AcGal-1 increased the expression of apoptosis proteins caspase-3, caspase-9, Bax, but reduced the expression of anti-apoptosis protein Bcl-2. AcGal-1 interacted with the membrane protein Annexin A2, and knockdown of Annexin A2 expression increased Bcl-2 but decreased Bax levels in AcGal-1-treated cells. Moreover, AcGal-1 increased JNK phosphorylation and the inhibition of JNK phosphorylation in AcGal-1-treated cells decreased the expression of caspase-3, -9, Bax and almost restored Bcl-2 to the level observed in control cells. CONCLUSIONS: AcGal-1 can induce the apoptosis of macrophages by binding to Annexin A2 and activating JNK downstream the apoptotic signaling pathway.

El riesgo de parasitismo por Angiostrongylus cantonensis: una problemática reemergente en Cuba / The risk of parasitism by Angiostrongylus cantonensis: a re-emerging problem in Cuba / O risco de parasitismo devido a Angiostrongylus cantonensis: um problema reemergente em Cuba

RESUMEN Introducción: El riesgo de parasitismo por Angiostrongylus cantonensis transmitido por el caracol gigante africano es una problemática reemergente en Cuba. Objetivo: Sistematizar contenidos esenciales relacionados con el caracol gigante africano y el parásito Angiostrongylus cantonensis, el riesgo de meningitis eosinofílica y su manejo. Método: En el Hospital General Docente "Dr. Agostinho Neto", entre septiembre y diciembre de 2019 se hizo una revisión narrativa sobre el tema a través de una búsqueda en bases de datos electrónicas (Biblioteca Virtual en Salud): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Resultados: La información se estructuró en caracterización del caracol gigante africano y el riesgo de infección por Angiostrongylus cantonensis en Cuba, patogénesis y epidemiologia de la angiostrongylosis, y diagnóstico y tratamiento de la meningitis eosinofílica por este nemátodo. Se identificaron controversias sobre los criterios diagnósticos, el protocolo de actuación para su prevención y rehabilitación, y la carencia de un instrumento para estratificar el riesgo de esta infección. Conclusiones: Se sistematizaron contenidos esenciales sobre el caracol gigante africano, lo que posibilita la preparación de los profesionales para incrementar la percepción del riesgo de infección por Angiostrongylus cantonensis en la población.

ABSTRACT Introduction: The risk of parasitism by Angiostrongylus cantonensis transmitted by the giant African land snail, Lissachatina fulica is a re-emerging problem in Cuba. Objective: Systematize essential contents related to the giant African land snail and the parasite Angiostrongylus cantonensis, the risk of eosinophilic meningitis and its management. Method: A narrative review was made on the subject in the Teaching General Hospital "Dr. Agostinho Neto", between September and December 2019 through a search in electronic databases (Virtual Health Library): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Results: The information was structured in the characterization of the African giant land snail and the risk of infection by Angiostrongylus cantonensis in Cuba, pathogenesis and epidemiology of angiostrongylosis, and diagnosis and treatment of eosinophilic meningitis by this nematode. Controversies were identified regarding the diagnostic criteria, the protocol of action for its prevention and rehabilitation, and the lack of an instrument to stratify the risk of this infection. Conclusions: Essential content on the giant African land snail was systematized, enabling the preparation of professionals to increase the perception of the risk of infection by Angiostrongylus cantonensis in the population.

RESUMO Introdução: O risco de parasitismo causado por Angiostrongylus cantonensis transmitido pelo caracol gigante africano é um problema reemergente em Cuba. Objetivo: Sistematizar conteúdos essenciais relacionados ao caracol gigante africano e ao parasita Angiostrongylus cantonensis, ao risco de meningite eosinofílica e seu manejo. Método: No Hospital Geral de Ensino "Dr. Agostinho Neto", entre setembro e dezembro de 2019, foi realizada uma revisão narrativa do assunto através de uma busca em bases de dados eletrônicas (Biblioteca Virtual em Saúde): LILACS, PubMed, SciELO, RedALyC, Scopus, Cochrane. Resultados: As informações foram estruturadas na caracterização do caracol gigante africano e no risco de infecção por Angiostrongylus cantonensis em Cuba, patogênese e epidemiologia da angiostrongilose, diagnóstico e tratamento da meningite eosinofílica por esse nematóide. Foram identificadas controvérsias sobre os critérios diagnósticos, o protocolo de ação para sua prevenção e reabilitação e a falta de um instrumento para estratificar o risco dessa infecção. Conclusões: Foram sistematizados conteúdos essenciais sobre o caracol gigante africano, o que possibilita a preparação de profissionais para aumentar a percepção do risco de infecção por Angiostrongylus cantonensis na população.