RESUMO
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.
Assuntos
Albendazol , Microscopia Eletrônica de Varredura , Mifepristona , Progesterona , Trichinella spiralis , Triquinelose , Animais , Triquinelose/tratamento farmacológico , Camundongos , Trichinella spiralis/efeitos dos fármacos , Trichinella spiralis/ultraestrutura , Mifepristona/uso terapêutico , Mifepristona/farmacologia , Albendazol/uso terapêutico , Albendazol/farmacologia , Feminino , Fator A de Crescimento do Endotélio Vascular , Imuno-Histoquímica , Mastócitos/efeitos dos fármacos , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia , MasculinoRESUMO
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.
Assuntos
Armadilhas Extracelulares , Evasão da Resposta Imune , Trichinella spiralis , Animais , Trichinella spiralis/fisiologia , Trichinella spiralis/imunologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/metabolismo , Camundongos , Proteínas de Helminto/metabolismo , Larva/imunologia , Larva/parasitologiaRESUMO
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.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias Orbitárias , Rabdomioma , Triquinelose , Humanos , Masculino , Rabdomioma/cirurgia , Rabdomioma/diagnóstico , Rabdomioma/diagnóstico por imagem , Triquinelose/diagnóstico , Pré-Escolar , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Neoplasias Orbitárias/diagnóstico , Animais , Trichinella spiralis/isolamento & purificação , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/cirurgia , Infecções Oculares Parasitárias/parasitologiaRESUMO
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.
RESUMO
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.
Assuntos
Transcriptoma , Trichinella spiralis , Trichinella , Animais , Trichinella spiralis/genética , Trichinella/genética , Genômica/métodos , Genoma Helmíntico , Perfilação da Expressão Gênica/métodos , Larva/genética , Larva/metabolismo , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Especificidade da Espécie , Interações Hospedeiro-Parasita/genética , Triquinelose/parasitologia , Triquinelose/genéticaRESUMO
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 (25.3â¯%). The dominant species was T. spiralis, identified in 28 samples (60â¯%), T. britovi was found in 13 samples (28â¯%), while for six samples (12â¯%) 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 (22.9â¯%) than in SEEP (26.7â¯%) (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.
RESUMO
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.
Assuntos
Artrite Experimental , Linfócitos T CD4-Positivos , Diferenciação Celular , Células Th17 , Trichinella spiralis , Tropomiosina , Animais , Trichinella spiralis/imunologia , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Experimental/tratamento farmacológico , Camundongos , Diferenciação Celular/efeitos dos fármacos , Tropomiosina/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th1/imunologia , Masculino , Proteínas de Helminto/farmacologia , Proteínas de Helminto/uso terapêutico , Proteínas de Helminto/imunologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos DBARESUMO
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.
Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Interleucina-9 , SARS-CoV-2 , COVID-19/imunologia , COVID-19/prevenção & controle , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Animais , Humanos , Interleucina-9/imunologia , Interleucina-9/metabolismo , SARS-CoV-2/imunologia , Citocinas/metabolismo , Citocinas/imunologia , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologiaRESUMO
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.
Assuntos
Asma , Proteínas de Helminto , Ovalbumina , Trichinella spiralis , Trichinella spiralis/imunologia , Animais , Asma/imunologia , Asma/tratamento farmacológico , Camundongos , Ovalbumina/imunologia , Proteínas de Helminto/imunologia , Proteínas de Helminto/farmacologia , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Feminino , Citocinas/metabolismo , Citocinas/imunologia , Imunoglobulina E/imunologia , Pulmão/imunologia , Pulmão/parasitologia , Pulmão/patologia , Linfócitos T Reguladores/imunologia , Hipersensibilidade/imunologia , Hipersensibilidade/tratamento farmacológico , Células Th17/imunologiaRESUMO
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.
Assuntos
Estresse do Retículo Endoplasmático , Células Epiteliais , Estresse Oxidativo , Serpinas , Trichinella spiralis , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Trichinella spiralis/fisiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Suínos , Serpinas/metabolismo , Serpinas/genética , Inibidores de Serina Proteinase/farmacologia , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética , Jejuno/efeitos dos fármacosRESUMO
Parasitic helminth Trichinella spiralis (Ts) induce mixed Th1/Th2 response with predominant type 2 immune responses, with protective immunity mediated by interleukin (IL)-4, IL-5, and IL-13. ß-Glucan (BG) has been shown to have the ability to induce trained immunity, confers non-specific protection from secondary infections. However, whether BG-induced trained immunity played a role in protective type 2 immunity against Ts infection is unclear. In this study, BG was administered five days before Ts infection to induce trained immunity. Our findings demonstrate that BG pretreatment effectively reduced the number of T. spiralis adults and muscle larvae, whereas inhibition of trained immunity abolished the effect of BG. Additionally, we observed a significant increase in goblet cells and mucus production as evidenced by Alcian blue periodic acid-Schiff staining. Furthermore, quantitative real-time PCR analysis revealed a significant upregulation of IL-4, IL-5, and IL-13 expression in response to BG. Conversely, the inhibitor of trained immunity reversed these effects, suggesting that BG-induced trained immunity confers strong protection against Ts infection. In conclusion, these findings suggest that BG-induced trained immunity may play a role in protection against infections caused by other helminths.
RESUMO
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.
RESUMO
Phylogenetic evidence indicates that free-living nematodes gave rise to parasitic nematodes where parasitism evolved independently at least 15 times. The high level of genetic and biological diversity among parasites dictates an equally high level of diversity in the transition to parasitism. We previously hypothesized that horizontal gene transfer (HGT) played an important role in the evolution of parasitism among early ancestors of Trichinella, mediated by an interplay of ecological and evolutionary pathways that contributed to persistence and diversification. We propose that host selection may have been associated with the metabolism of ammonia and engender a new paradigm whereby the reprogrammed nurse cell is capable of generating cyanate thereby enabling the importance of the Trichinella cyanase in the longevity of the cell. Parasites and parasitism have revealed considerable resilience against a backdrop of climate change and environmental perturbation. Here we provide a putative link between key periods in the evolution of Trichinella and major geological and climatological events dating back 500 million years. A useful lens for exploring such ideas, the Stockholm Paradigm, integrates Ecological Fitting (a foundation for host colonization and diversification), the Oscillation Hypothesis (recurring shifts between trends in generalization and specialization relative to host range), the Geographic Mosaic Theory of Coevolution (microevolutionary co-adaptive processes), and the Taxon Pulse Hypothesis (alternating events of biotic expansion i.e., exploitation in evolutionary and ecological time). Here we examine how one or more of these interactive theories, in a phylogenetic-historical context and in conjunction with HGT, may help explain the scope and depth of diversity among Trichinella genotypes.
RESUMO
Hyperactivation of pro-inflammatory type 1 cytokines (e.g., tumor necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ]) mirrors the inflammation of coronavirus disease 2019. Helminths could alleviate excessive immune responses. Here, helminth Trichinella spiralis (Ts) infection was shown to protect against TNF-α- and IFN-γ-induced shock. Mechanistically, Ts-induced protection was interleukin-9 (IL-9) dependent but not IL-4Rα. Recombinant IL-9 treatment not only improved the survival of wild-type mice with TNF-α- and IFN-γ-induced shock but also that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected K18-human angiotensin-converting enzyme 2 (hACE2) mice, emphasizing the significance of IL-9 in alleviating cytokine storm syndromes during SARS-CoV-2 infection. Interestingly, Ts excretory/secretory (TsES)-induced protection was also observed in SARS-CoV-2 infection, indicating that identifying anti-inflammatory molecules from TsES could be a novel way to mitigate adverse pathological inflammation during pathogen infection.IMPORTANCESevere coronavirus disease 2019 (COVID-19) is linked to cytokine storm triggered by type 1 pro-inflammatory immune responses. TNF-α and IFN-γ shock mirrors cytokine storm syndromes, including COVID-19. Helminths (e.g., Trichinella spiralis, Ts) can potently activate anti-inflammatory type 2 immune response. Here, we found that helminth Ts-induced protection against TNF-α and IFN-γ shock was IL-9 dependent. Treatment with recombinant IL-9 could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in K18-hACE2 mice. Helminth Ts excretory/secretory (TsES) products also ameliorated SARS-CoV-2 infection-related cytokine storm. In conclusion, our study emphasizes the significance of IL-9 in protecting from cytokine storm syndromes associated with SARS-CoV-2 infection. Anti-inflammatory molecules from TsES could be a new source to mitigate adverse pathological inflammation associated with infections, including COVID-19.
Assuntos
COVID-19 , Síndrome da Liberação de Citocina , Interleucina-9 , SARS-CoV-2 , Trichinella spiralis , Animais , COVID-19/imunologia , Camundongos , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Trichinella spiralis/imunologia , SARS-CoV-2/imunologia , Humanos , Interleucina-9/metabolismo , Interleucina-9/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Modelos Animais de Doenças , Triquinelose/imunologia , Feminino , Camundongos Endogâmicos C57BL , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genéticaRESUMO
Lung cancer is a dangerous disease that is lacking in an ideal therapy. Here, we evaluated the anti-lung cancer effect in nude mice of a fully human single-chain antibody (scFv) against the associated antigen 7 transmembrane receptor (Ts7TMR), which is also called G protein-coupled receptor, between A549 cells and Trichinella spiralis (T. spiralis). Our data showed that anti-Ts7TMR scFv could inhibit lung cancer growth in a dose-dependent manner, with a tumour inhibition rate of 59.1%. HE staining did not reveal any obvious tissue damage. Mechanistically, immunohistochemical staining revealed that the scFv down-regulated the expression of PCNA and VEGF in tumour tissues. Overall, this study found that anti-Ts7TMR scFv could inhibit A549 lung cancer growth by suppressing cell proliferation and angiogenesis, which may provide a new strategy for treating lung cancer.
Assuntos
Neoplasias Pulmonares , Anticorpos de Cadeia Única , Trichinella spiralis , Animais , Humanos , Camundongos , Células A549 , Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Camundongos Nus , Neovascularização Patológica/imunologia , Antígeno Nuclear de Célula em Proliferação/imunologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/farmacologia , Trichinella spiralis/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The gut microbiota has coevolved with the host for hundreds of millions of years, playing a beneficial role in host health. Human parasitic helminths are widespread and pose a pervasive global public health issue. Although Type 2 immunity provides partial resistance to helminth infections, the composition of the gut microbiota can change correspondingly. Therefore, it raises the question of what role the gut microbiota plays during helminth infection. Akkermansia muciniphila has emerged as a notable representative of beneficial microorganisms in the gut microbiota. Recent studies indicate that A. muciniphila is not merely associated with helminth infection but is also causally linked to infection. Here, we provide an overview of the crosstalk between A. muciniphila and enteric helminth infection. Our goal is to enhance our understanding of the interplay among A. muciniphila, helminths, and their hosts while also exploring the potential underlying mechanisms.
Assuntos
Akkermansia , Microbioma Gastrointestinal , Animais , Humanos , Helmintíase/imunologia , Helmintos/imunologia , Helmintos/genética , Verrucomicrobia/genética , Verrucomicrobia/imunologiaRESUMO
The species of the genus Trichinella are etiological agents distributed all over the world and are able to infect mammals, birds, and reptiles. Trichinella spiralis is the species most adapted to domestic and wild pigs and is also the most important etiological agent of trichinellosis. The wild boar (Sus scrofa) is a nocturnal omnivorous mammal belonging to the Suidae family. S. scrofa has a great appetite and its diet includes a variety of small prey such as mice, rats, and other rodents, as well as carcasses of larger animals. The aim of this study was the identification and the molecular characterization of Trichinella larvae isolated from the muscle tissue of S. scrofa specimens collected in different counties of Romania. The muscle samples were examined by artificial digestion and the larvae identified at the species level by multiplex PCR. T. spiralis, a species that is able to infect a considerable number of different host species including humans, was identified. In Romania, S. scrofa is an important reservoir species for T. spiralis and plays an important role in linking the domestic and the wild cycle of Trichinella, with serious repercussions for human health.
RESUMO
Beneficial/probiotic strains protect the host from pathogens by competitive displacement and production of antibacterial substances, i.e., bacteriocins. The antiparasitic potential of bacteriocins/enterocins and their producing strains in experimental murine trichinellosis were tested as a new therapeutic strategy. Enterocin M and Durancin-like and their producers Enterococcus faecium CCM8558 and Enterococcus durans ED26E/7 were administered daily to mice that were challenged with Trichinella spiralis. Our study confirmed the antiparasitic effect of enterocins/enterococci, which reduced the number of adults in the intestine (Enterocin M-43.8%, E. faecium CCM8558-54.5%, Durancin-like-16.4%, E. durans ED26E/7-35.7%), suppressed the Trichinella reproductive capacity ex vivo (Enterocin M-61%, E. faecium CCM8558-74%, Durancin-like-38%, E. durans ED26E/7-66%), and reduced the number of muscle larvae (Enterocin M-39.6%, E. faecium CCM8558-55.7%, Durancin-like-15%, E. durans ED26E/7-36.3%). The direct effect of enterocins on Trichinella fecundity was documented by an in vitro test in which Durancin-like showed a comparable reducing effect to Enterocin M (40-60%) in contrast to the ex vivo test. The reducing activity of T.spiralis infection induced by Enterocin M was comparable to its strain E. faecium CCM8558; Durancin-like showed lower antiparasitic activity than its producer E. durans ED26E/7.
RESUMO
Sepsis is a disorder of immune regulation caused by pathogenic microorganisms. A large number of inflammatory factors and inflammatory mediators are released, resulting in systemic inflammatory response disorder and acute lung injury (ALI). Helminths infection activate Th2 cytokines and immunomodulatory pathways, which have the function of anti-infection effector molecules. The early infection of Trichinella spiralis (T. spiralis) was mainly intestinal phase. In this study, we explored the effect of intestinal phase infection of T. spiralis on LPS-induced ALI. Compared with control mice, the serum and lung tissues of T. spiralis infected mice had a significant decrease of Th1 inflammatory cytokines, a significant increase of Th2 anti-inflammatory cytokines, and a significant decrease of inflammatory cell infiltration in lung tissue. These results suggest that T. spiralis during the intestinal phase can act on distal organs (lung) and reduce LPS-induced lung inflammation, providing evidence for a potential new pathway for immune-mediated disease in helminths and a possible role for intestinal worms in the gut-lung axis.
RESUMO
Trichinella spiralisis an uncommon parasitic disease contracted through the consumption of undercooked pork. We report the case of a 59-year-old man with a history of bicuspid aortic valve with recent travel to the Philippines and consumption of raw pork presenting with progressive myalgia and hypereosinophilia (nadir 12,940/uL) in profound cardiogenic shock in the setting of critical aortic stenosis. He underwent emergent balloon valvuloplasty, which was complicated by aortic insufficiency. This necessitated a transcatheter aortic valve replacement. However, despite hemodynamic stabilization, he developed catastrophic eosinophilic myocarditis, complicated by cardiac arrest from ventricular tachycardia. A rectus femoris muscle biopsy confirmed the diagnosis, showing a T. spiralis parasite and significant eosinophilic infiltration. Empiric treatment with albendazole, ivermectin, and methylprednisolone resulted in the significant resolution of symptoms and the liberalization of critical illness. This case highlights the challenges of diagnosing the underlying etiologies of hypereosinophilia and/or eosinophilic myocarditis, underscoring the importance of considering parasitic etiologies, particularly in endemic regions or in patients who have a significant travel history to such areas. Prompt diagnosis and treatment are essential to prevent morbidity and mortality.