RESUMEN

No approved effective therapy for non-alcoholic steatohepatitis (NASH) is currently available. Trichinella spiralis (T. spiralis) infection and their products have positive impact on several metabolic diseases. Considering, we firstly investigated the effects of the T. spiralis-derived Excretory-Secretory antigens (ESA) on high fat diet (HFD)-induced NASH mouse models. To further elucidate the mechanism of action, HepG2 cells were incubated with palmitic acid (PA) to construct NASH-like cell model, and then the culture medium supernatant collected from ESA-treated macrophages was applied to intervene the cell model in vitro. In NASH mouse models, ESA significantly alleviated hepatic steatosis and hepatic inflammation, as reflected by reducing pro-inflammatory cytokines and inactivating TLR4/MYD88/NF-κB pathway and NLRP3 inflammasome. Meanwhile, the HFD-induced oxidative stress was restored by ESA through lessening the level of MDA, increasing the activity of T-SOD and enhancing Nrf2 signaling-related proteins, including p-Nrf2, NQO1, HO-1, GPX4, and p-AMPK. Notably, ESA preferentially promoted macrophages polarization toward M2 anti-inflammatory phenotype in vivo and vitro. Moreover, in vitro, intervention of PA-treated HepG2 cells with medium supernatant of ESA-treated macrophages attenuated lipid accumulation, inflammation, as well as oxidative stress. In conclusion, T. spiralis-derived ESA may serve as a novel promising candidate for the treatment of NASH via its properties of driving macrophage anti-inflammatory activity.

RESUMEN

Although helminth parasites have different life cycles, their hosts share similar immune responses involving Th2 cell-type. Here, we extracted proteins from the larvae of Anisakis simplex complex and Trichinella spiralis to identify common and specific antigens (or allergens) associated with the Th2 immune response. We performed two-dimensional electrophoresis analysis and Matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) experiments. We found 13 potentially immunogenic proteins, which included 5 spots specific to T. spiralis and 8 common to T. spiralis and A. simplex, by tandem mass spectrometry. These molecules were identified structurally as actin, tropomyosin, col cuticle N domain-containing protein, and heat shock proteins. We also identified molecules related to parasite-host immune modulation and interactions. Our results may contribute to reveal potential roles of immunological proteins in parasite-derived immune modulation.

Asunto(s)

Anisakis , Proteínas del Helminto , Proteoma , Trichinella spiralis , Animales , Proteoma/inmunología , Proteínas del Helminto/inmunología , Trichinella spiralis/inmunología , Anisakis/inmunología , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/análisis , Electroforesis en Gel Bidimensional , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Interacciones Huésped-Parásitos/inmunología , Larva/inmunología , Espectrometría de Masas en Tándem

RESUMEN

Trichinellosis, caused by 13 species/subspecies/genotypes in the nematode genus Trichinella, is a worldwide zoonosis. In the United States, trichinellosis was of historical and economic significance because of European restrictions on the import of U.S. pork. Before the advent of effective protective measures, most cases of trichinellosis were derived from consumption of undercooked or inadequately processed, infected pork. Research conducted at the United States Department of Agriculture (USDA) since 1891, and policies established by USDA regulatory agencies, have helped to reduce Trichinella infections in commercially raised domestic pigs to negligible levels. Here, we review the history of this scientific progress, placing special emphasis on research conducted at the USDA's Beltsville Agricultural Research Center.

RESUMEN

Trichinella infections have been eliminated from pork where pigs are raised in biosecure facilities, but wildlife infections persist. Trichinella murrelli is the primary zoonotic species in wild carnivores in the United States, having been identified in several species of omnivores and carnivores. Here, we document its occurrence in seven of 21 (33.3%) red foxes (Vulpes vulpes) from six counties in Pennsylvania. Encysted Trichinella larvae were detected in muscle squashes (<5 g samples) of all seven foxes, and in histological sections of the tongue and limb muscle of three. Larvae from muscle squashes were pooled and tested in a multiplex PCR capable of differentiating all Trichinella species native to the USA; all samples contained only T. murrelli. This is the first identification of T. murrelli in red foxes from Pennsylvania, and the first such survey performed in the last three decades. Results indicate that Trichinella remains endemic in Pennsylvania wildlife and a threat to the health of those who consume wild game.

Asunto(s)

Zorros , Trichinella , Triquinelosis , Animales , Zorros/parasitología , Triquinelosis/veterinaria , Triquinelosis/parasitología , Triquinelosis/epidemiología , Pennsylvania/epidemiología , Trichinella/aislamiento & purificación , Trichinella/clasificación , Femenino , Animales Salvajes/parasitología , Masculino , Larva/clasificación

RESUMEN

The Trichinella spiralis novel cystatin (TsCstN) inhibits cathepsin L (CatL) activity and inflammation of macrophages during lipopolysaccharide (LPS) induction. To identify the protease inhibitory region, this study applied an in silico modeling approach to simulate truncation sites of TsCstN (Ts01), which created four truncated forms, including TsCstN∆1-39 (Ts02), TsCstN∆1-71 (Ts03), TsCstN∆1-20, ∆73-117 (Ts04), and TsCstN∆1-20, ∆42-117 (Ts05). The superimposition of these truncates modeled with AlphaFold Colab indicated that their structures were more akin to Ts01 than those modeled with I-TASSER. Moreover, Ts04 exhibited the closest resemblance to the structure of Ts01. The recombinant Ts01 (rTs01) and truncated proteins (rTs02, rTs03, and rTs04) were successfully expressed in a prokaryotic expression system while Ts05 was synthesized, with sizes of approximately 14, 12, 8, 10, and 2.5 kDa, respectively. When determining the inhibition of CatL activity, both rTs01 and rTs04 effectively reduced CatL activity in vitro. Thus, the combination of the α1 and L1 regions may be sufficient to inhibit CatL. This study provides comprehensive insights into TsCstN, particularly regarding its protein function and inhibitory domains against CatL.

Asunto(s)

Cistatinas , Trichinella spiralis , Trichinella spiralis/genética , Trichinella spiralis/metabolismo , Animales , Cistatinas/metabolismo , Cistatinas/química , Cistatinas/genética , Catepsina L/metabolismo , Proteínas del Helminto/química , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Modelos Moleculares , Dominios Proteicos , Ratones , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Lipopolisacáridos/farmacología

RESUMEN

Muscles of 25 bobcats (Lynx rufus) from remote areas of Mississippi in 2017 were tested for parasites. Testing for Sarcocystis infections included microscopic examination of fresh unstained muscle squashes, pepsin digestion of hearts and tongues, and histological sections of paraffin-embedded tissues. Sarcocystis spp. infections were detected in the muscles of 21 (84%) by a combination of methods. Sarcocysts were detected in the unstained tongue squashes of 2 bobcats. Sarcocystis sp. bradyzoites were detected in the pepsin digests of 3 of 19 hearts, and 12 of 19 tongues. In paraffin-embedded histological sections, sarcocysts were detected in 7 of 25 hearts, 17 of 25 tongues, and 5 of 23 limb muscles. Based on the character of the cyst wall, at least 3 morphologic types of sarcocysts were detected: those with small spikes on the cyst wall, corresponding to Sarcocystis felis, those with long villar protrusions, corresponding to Sarcocystis neurona, and those lacking visible cyst wall protrusions, representing an unidentified type of sarcocyst. Myositis associated with sarcocysts was seen in the tongues of 3, and in the limb muscles of 1 bobcat. Multilocus genotyping of the DNA extracted from paraffin-embedded sections from 2 bobcats, employing 18S, 28S, COI, ITS-1, and 5.8S and rpoB genes, diagnosed Sarcocystis caninum, S. felis, Sarcocystis lutrae, and S. neurona. An encapsulated species of Trichinella was identified in the tongue of 1; it represents the first documented occurrences in bobcats from Mississippi. Taken together, these observations suggest intensive exposure of these wild carnivores to Trichinella tissue cysts, implies predation or scavenging on these tissues promotes parasite transmission, and raises caution concerning zoonotic risk when such meat is rendered for human consumption.

Asunto(s)

Lynx , Sarcocystis , Sarcocistosis , Lengua , Trichinella , Triquinelosis , Animales , Sarcocistosis/veterinaria , Sarcocistosis/parasitología , Sarcocystis/clasificación , Sarcocystis/aislamiento & purificación , Sarcocystis/genética , Lynx/parasitología , Mississippi , Triquinelosis/veterinaria , Triquinelosis/parasitología , Trichinella/aislamiento & purificación , Trichinella/clasificación , Trichinella/genética , Lengua/parasitología , Femenino , Masculino , Corazón/parasitología , Músculo Esquelético/parasitología , ADN Protozoario/aislamiento & purificación , ADN Protozoario/química , Prevalencia

RESUMEN

Biosecurity measures preventing exposure of pigs to rodents, wildlife, and contaminated feed or waste products reduce the risk of zoonotic Trichinella infection in pork. To understand the benefits of such measures in the United States, we conducted the first comprehensive survey of pigs produced under the Pork Quality Assurance Plus production standard, surveying 3,208,643 pork samples from twelve processing locations tested over a period of 54 months. We detected no Trichinella sp. positives in any of these pork samples, providing a 95% confidence in a Trichinella sp. prevalence of <1 in 1,000,000 for the processors represented by the study. These results are consistent with international guidelines for having a negligible risk to public health. Results obtained here should generalize to all PQA+ sources, as Trichinella sp. exposure risk is based on production guidelines that extend to the larger PQA+ population.

RESUMEN

Trichinella spp. are cosmopolitan parasites that infect a wide range of hosts, with wildlife being the main reservoir of these zoonotic nematodes, especially red foxes (Vulpes vulpes) and wolves (Canis lupus) due to their apex position in the food chain in most European countries. The aim of this study is to investigate the prevalence of Trichinella spp. in these wild canids and their epidemiological role in the Campania region (southern Italy). From 2017 to 2023, the carcasses of red foxes (n = 352) and wolves (n = 41) were collected as part of a health surveillance plan. Muscle samples were analysed individually by artificial digestion and four (1.1%) red foxes and nine (21.9%) wolves tested positive for Trichinella britovi. All Trichinella isolates were identified as T. britovi by multiplex PCR. Statistically significant differences in prevalence were found by province (p-value = 0.05) for red foxes and sampling years (p-value = 0.01) for wolves. The prevalence was lower in red foxes than in wolves, probably due to the longer life expectancy of wolves compared to red foxes and the role of wolves as apex predators compared to red foxes as meso-carnivores. The results obtained confirm the important role that these wild canids play in the circulation of the parasite.

Asunto(s)

Zorros , Trichinella , Triquinelosis , Lobos , Animales , Zorros/parasitología , Lobos/parasitología , Italia/epidemiología , Trichinella/aislamiento & purificación , Triquinelosis/epidemiología , Triquinelosis/veterinaria , Triquinelosis/parasitología , Prevalencia , Animales Salvajes/parasitología

RESUMEN

Trichinellosis is a zoonotic disease caused by Trichinella, with the main source of infection being the consumption of pork and pork-derived products. However, it can also be acquired from eating the meat from wild animals targeted for sport hunting. The objectives of this study were: 1) to develop and implement a molecular method for the identification of Sus scrofa (pig and wild boar) and Puma concolor (Puma) meat in sausages eaten raw, which were linked to trichinellosis outbreaks occurring in Córdoba, Buenos Aires and La Pampa provinces, Argentina, in 2010, 2021, and 2022, respectively; and 2) to identify the Trichinella species present in the food. Specific primers were designed for PCR amplification and nucleotide sequencing of a region of the mitochondrial cytochrome b gene from both host species. Samples from the mentioned outbreaks were analysed, and the molecular identification of Trichinella spp. larvae was also performed. Results of the species identification system revealed that sausages from Córdoba and Buenos Aires had a mixed composition of pork and puma meat, while those from La Pampa contained puma meat only. Trichinella spiralis was implicated in all three outbreaks. The species identification system developed and implemented in this study revealed two host species of Trichinella related to human cases, and alerts about the risk of zoonotic transmission to humans through infected puma meat.

Asunto(s)

Brotes de Enfermedades , Productos de la Carne , Puma , Sus scrofa , Triquinelosis , Animales , Triquinelosis/epidemiología , Triquinelosis/transmisión , Triquinelosis/parasitología , Productos de la Carne/parasitología , Argentina/epidemiología , Puma/parasitología , Porcinos , Sus scrofa/parasitología , Humanos , Trichinella spiralis/genética , Trichinella spiralis/aislamiento & purificación , Trichinella/genética , Trichinella/aislamiento & purificación , Trichinella/clasificación , Zoonosis/parasitología , Zoonosis/transmisión

RESUMEN

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host-parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin-with possible roles in modulating host immune responses and facilitating parasite survival-were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella-host interactions might offer possible avenues for developing new interventions against trichinellosis.

Asunto(s)

Transcriptoma , Trichinella spiralis , Trichinella , Animales , Trichinella spiralis/genética , Trichinella/genética , Genómica/métodos , Genoma de los Helmintos , Perfilación de la Expresión Génica/métodos , Larva/genética , Larva/metabolismo , Proteínas del Helminto/genética , Proteínas del Helminto/metabolismo , Especificidad de la Especie , Interacciones Huésped-Parásitos/genética , Triquinelosis/parasitología , Triquinelosis/genética

RESUMEN

Right up to now, there has not been an effective or safe therapy for trichinellosis. Thus, this study aimed to determine the efficacy of prophylactic and therapeutic regimens of progesterone and mifepristone on the intestinal and muscular phases of experimental Trichinella spiralis infection compared to albendazole. Seven distinct groups of mice were divided as follows: negative, positive, and drug control groups, as well as prophylactic and treatment groups using mifepristone and progesterone. Mice were sacrificed on the 7th and 37th days after infection. Treatment efficacy was evaluated using parasitological techniques, histopathological examination, immunohistochemical staining, and ultrastructural morphological analysis of adult worms by scanning electron microscopy. The mice groups received progesterone (300 ng/ml) and mifepristone (100 ng/ml). They demonstrated a significant improvement in intestinal and muscular inflammation and a statistically significant decline in the adult worm burden and encysted larvae (P < 0.001). Moreover, immunohistochemical staining of vascular endothelial growth factor and mucosal mast cell analyses were coincided with the obtained parasitological results. There was notable destruction and degeneration of the adult worm tegument by using both drugs. The current study pointed out that progesterone and mifepristone may provide new insights regarding the development of vaccines and drug protocols to treat trichinellosis through their combined action in reducing the inflammation, affecting the intestinal immune cell, and decreasing the adult worm burden, and larval capsule development.

Asunto(s)

Albendazol , Microscopía Electrónica de Rastreo , Mifepristona , Progesterona , Trichinella spiralis , Triquinelosis , Animales , Triquinelosis/tratamiento farmacológico , Ratones , Trichinella spiralis/efectos de los fármacos , Trichinella spiralis/ultraestructura , Mifepristona/uso terapéutico , Mifepristona/farmacología , Albendazol/uso terapéutico , Albendazol/farmacología , Femenino , Factor A de Crecimiento Endotelial Vascular , Inmunohistoquímica , Mastocitos/efectos de los fármacos , Antihelmínticos/uso terapéutico , Antihelmínticos/farmacología , Masculino

RESUMEN

Rhabdomyoma of the orbit is a rare tumor with very few cases reported in the literature. We herein describe a 5-year-old boy who presented to us with a deviation of his left eye. Magnetic Resonance Imaging (MRI) showed a well-defined homogeneous intraconal mass in the superomedial aspect compressing the optic nerve. An excision biopsy was performed and the diagnosis of rhabdomyoma was confirmed on histopathology and immunohistochemistry with a coincidental finding of Trichinella spiralis larvae within the excised specimen. We report this phenomenon in two rare diseases with a predilection for striated muscle occurring simultaneously in a single patient.

Asunto(s)

Imagen por Resonancia Magnética , Neoplasias Orbitales , Rabdomioma , Triquinelosis , Humanos , Masculino , Rabdomioma/cirugía , Rabdomioma/diagnóstico , Rabdomioma/diagnóstico por imagen , Triquinelosis/diagnóstico , Preescolar , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Orbitales/patología , Neoplasias Orbitales/cirugía , Neoplasias Orbitales/diagnóstico , Animales , Trichinella spiralis/aislamiento & purificación , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/cirugía , Infecciones Parasitarias del Ojo/parasitología

RESUMEN

Epidemiologic monitoring of wild animals is always an important step in defining potential zoonoses that can threaten humans. Particular emphasis should be given to those zoonotic agents permanently cycling within wild animal populations and represent a permanent reservoir for other wild or domesticated animals that can be direct sources of disease for humans. In Croatia, there are two European jackal populations: the Dalmatian population (DP) that has been inhabiting the islands and coastal area along the Adriatic Sea since medieval times, and the South East European population (SEEP) that is found in continental Croatia. Research on Trichinella infections in jackal populations in Croatia was conducted from 2008 to 2022. During this 15-year period, we tested 186 jackal samples and confirmed infection in 47 individuals (25.3 %). The dominant species was T. spiralis, identified in 28 samples (60 %), T. britovi was found in 13 samples (28 %), while for six samples (12 %) the PCR test was unsuccessful. In both populations, the Trichinella species of the domestic cycle (T. spiralis) was found, though in varying ratios: in DP the ratio of identified species was 10:6 in favour of T. britovi, as opposed to 22:3 in favour of T. spiralis in SEEP. The frequency of infection with parasites from the genus Trichinella was significantly different in DP (22.9 %) than in SEEP (26.7 %) (p<0.001), while the larval count in analysed tissue did not differ by type of Trichinella species (p=0.1028). Infected jackals were found in nine of ten tested counties. The results were analysed statistically and the origin of tested and positive samples shown on a map of Croatia. Based on these findings, both jackal populations can be considered to represent an exceptionally important indicators of parasites from the genus Trichinella in Croatia, both for the sylvatic and domestic cycles. There is an evident need for epidemiological monitoring for members of both populations.

RESUMEN

In this study, serological screening for Toxoplasma gondii, Trichinella spp., and SARS-CoV-2 in domestic cats was conducted, aiming to identify their exposure to the mentioned pathogens and to assess the risk of potential human infection. In total, serum samples from 481 (310 owned and 171 shelter cats) were collected in Bratislava from September 2020 to September 2021, a period that included the initial outbreak wave of the COVID-19 pandemic. The study showed a 37.4% (135/441) seroprevalence of T. gondii with a slightly lower seropositivity in shelter cats (35.9%; 61/170) than in owned cats (38.4%; 104/271), but this difference was not statistically significant. Overall, the seroprevalence of Trichinella spp. was 2.0% (9/441), with animals from shelters being positive but not significantly more often (2.9%; 5/170) than owned cats (1.5%; 4/271). SARS-CoV-2 antibodies were detected in 2.7% (13/481) of cat sera (2.9% in shelter cats; 2.6% in owned cats). Among ten samples positive by virus neutralisation assay, two were positive for the B.1 variant. The presence of the SARS-CoV-2 virus in buccal and rectal swabs (n = 239) was not detected. The seroprevalence of almost 40% for T. gondii in cats suggests a non-negligible risk of human infection. The study confirmed the possibility of Trichinella spp. infection in cats, and thus the possibility of infection spreading between the sylvatic and synanthropic cycle via this animal species. The presented results also showed that the SARS-CoV-2 virus is likely to circulate in cat populations in Slovakia, not only in cats that may have been in contact with infected persons, but also in shelter cats.

RESUMEN

BACKGROUND: Trichinella spiralis (T. spiralis) is a parasitic helminth that causes a globally prevalent neglected zoonotic disease, and worms at different developmental stages (muscle larvae, adult worms, newborn larvae) induce immune attack at different infection sites, causing serious harm to host health. Several innate immune cells release extracellular traps (ETs) to entrap and kill most pathogens that invade the body. In response, some unicellular pathogens have evolved a strategy to escape capture by ETs through the secretion of nucleases, but few related studies have investigated multicellular helminths. RESULTS: In the present study, we observed that ETs from neutrophils capture adult worms of T. spiralis, while ETs from macrophages trap muscle larvae and newborn larvae, and ETs had a killing effect on parasites in vitro. To defend against this immune attack, T. spiralis secretes plancitoxin-1, a DNase II-like protein, to degrade ETs and escape capture, which is essential for the survival of T. spiralis in the host. CONCLUSIONS: In summary, these findings demonstrate that T. spiralis escapes ET-mediated capture by secreting deoxyribonuclease as a potential conserved immune evasion mechanism, and plancitoxin-1 could be used as a potential vaccine candidate.

Asunto(s)

Trampas Extracelulares , Evasión Inmune , Trichinella spiralis , Animales , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Proteínas del Helminto/metabolismo , Larva/inmunología , Larva/parasitología , Trichinella spiralis/fisiología , Trichinella spiralis/inmunología

RESUMEN

A recent study published in mBio by Cao et al. demonstrated that the helminth Trichinella sprialis (Ts) alleviates COVID-19-related cytokine storms in an IL-9-dependent way (Z. Cao, J. Wang, X. Liu, Y. Liu, et al., mBio 15:e00905-24, 2024, https://doi.org/10.1128/mbio.00905-24). A cytokine storm is a severe immune response characterized by the overproduction of proinflammatory cytokines, such as TNF-α and IFN-γ, leading to tissue damage and mortality in COVID-19 patients. This study indicated that IL-9 is crucial in protecting against cytokine storm syndromes associated with SARS-CoV-2 infection and proposed that anti-inflammatory molecules from Ts excretory/secretory (TsES) products could be a novel source for treating such illnesses.

Asunto(s)

COVID-19 , Síndrome de Liberación de Citoquinas , Interleucina-9 , SARS-CoV-2 , COVID-19/inmunología , COVID-19/prevención & control , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/prevención & control , Animales , Humanos , Interleucina-9/inmunología , Interleucina-9/metabolismo , SARS-CoV-2/inmunología , Citocinas/metabolismo , Citocinas/inmunología , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/inmunología

RESUMEN

Trichinellosis is a parasitic zoonotic disease transmitted through the consumption of meat from animals infected with Trichinella spp. nematodes. In North America, human trichinellosis is rare and is most commonly acquired through consumption of wild game meat. In July 2022, a hospitalized patient with suspected trichinellosis was reported to the Minnesota Department of Health. One week before symptom onset, the patient and eight other persons shared a meal that included bear meat that had been frozen for 45 days before being grilled and served rare with vegetables that had been cooked with the meat. Investigation identified six trichinellosis cases, including two in persons who consumed only the vegetables. Motile Trichinella larvae were found in remaining bear meat that had been frozen for >15 weeks. Molecular testing identified larvae from the bear meat as Trichinella nativa, a freeze-resistant species. Persons who consume meat from wild game animals should be aware that that adequate cooking is the only reliable way to kill Trichinella parasites and that infected meat can cross-contaminate other foods.

RESUMEN

BACKGROUND: For decades, studies have demonstrated the anti-inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta-like protein (SUCLA-ß) derived from Trichinella spiralis, a crucial excretory product of this parasite. OBJECTIVE: To explore the therapeutic potential of SUCLA-ß in alleviating and controlling ovalbumin (OVA)-induced allergic asthma, as well as its influence on host immune modulation. METHODS: In this research, we utilized the rTs-SUCLA-ß protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre- and post-challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs. RESULTS: Treatment with rTs-SUCLA-ß demonstrated efficacy in ameliorating OVA-induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA-specific Immunoglobulin E, interferon-γ, interleukin (IL)-9, and IL-17A, along with an elevation in IL-10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Our data revealed that T. spiralis-derived Ts-SUCLA-ß protein may inhibit the allergic airway inflammation by regulating host immune responses.

Asunto(s)

Asma , Proteínas del Helminto , Ovalbúmina , Trichinella spiralis , Trichinella spiralis/inmunología , Animales , Asma/inmunología , Asma/tratamiento farmacológico , Ratones , Ovalbúmina/inmunología , Proteínas del Helminto/inmunología , Proteínas del Helminto/farmacología , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad , Femenino , Citocinas/metabolismo , Citocinas/inmunología , Inmunoglobulina E/inmunología , Pulmón/inmunología , Pulmón/parasitología , Pulmón/patología , Linfocitos T Reguladores/inmunología , Hipersensibilidad/inmunología , Hipersensibilidad/tratamiento farmacológico , Células Th17/inmunología

RESUMEN

Endoplasmic reticulum stress (ERS) and oxidative stress (OS) are adaptive responses of the body to stressor stimulation. Although it has been verified that Trichinella spiralis (T. spiralis) can induce ERS and OS in the host, their association is still unclear. Therefore, this study explored whether T. spiralis-secreted serpin-type serine protease inhibitor (TsAdSPI) is involved in regulating the relationship between ERS and OS in the host intestine. In this study, mice jejunum and porcine small intestinal epithelial cells (IECs) were detected using qPCR, western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and detection kits. The results showed that ERS- and OS-related indexes changed significantly after TsAdSPI stimulation, and Bip was located in IECs, indicating that TsAdSPI could induce ERS and OS in IECs. After the use of an ERS inhibitor, OS-related indexes were inhibited, suggesting that TsAdSPI-induced OS depends on ERS. When the three ERS signalling pathways, ATF6, IRE1, and PERK, were sequentially suppressed, OS was only regulated by the PERK pathway, and the PERK-eif2α-CHOP-ERO1α axis played a key role. Similarly, the expression of ERS-related indexes and the level of intracellular Ca2+ were inhibited after adding the OS inhibitor, and the expression of ERS-related indexes decreased significantly after inhibiting calcium transfer. This finding indicated that TsAdSPI-induced OS could affect ERS by promoting Ca2+ efflux from the endoplasmic reticulum. The detection of the ERS and OS sequences revealed that OS occurred before ERS. Finally, changes in apoptosis-related indexes were detected, and the results indicated that TsAdSPI-induced ERS and OS could regulate IEC apoptosis. In conclusion, TsAdSPI induced OS after entering IECs, OS promoted ERS by enhancing Ca2+ efflux, and ERS subsequently strengthened OS by activating the PERK-eif2α-CHOP-ERO1α axis. ERS and OS induced by TsAdSPI synergistically promoted IEC apoptosis. This study provides a foundation for exploring the invasion mechanism of T. spiralis and the pathogenesis of host intestinal dysfunction after invasion.

Asunto(s)

Estrés del Retículo Endoplásmico , Células Epiteliales , Estrés Oxidativo , Serpinas , Trichinella spiralis , Animales , Estrés del Retículo Endoplásmico/efectos de los fármacos , Trichinella spiralis/fisiología , Ratones , Estrés Oxidativo/efectos de los fármacos , Porcinos , Serpinas/metabolismo , Serpinas/genética , Inhibidores de Serina Proteinasa/farmacología , Proteínas del Helminto/metabolismo , Proteínas del Helminto/genética , Yeyuno/efectos de los fármacos

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4+ T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4+ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4+ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4+ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4+ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4+ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases.

Asunto(s)

Artritis Experimental , Linfocitos T CD4-Positivos , Diferenciación Celular , Células Th17 , Trichinella spiralis , Tropomiosina , Animales , Trichinella spiralis/inmunología , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Experimental/tratamiento farmacológico , Ratones , Diferenciación Celular/efectos de los fármacos , Tropomiosina/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Células TH1/inmunología , Masculino , Proteínas del Helminto/farmacología , Proteínas del Helminto/uso terapéutico , Proteínas del Helminto/inmunología , Artritis Reumatoide/inmunología , Artritis Reumatoide/tratamiento farmacológico , Linfocitos T Reguladores/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos DBA