RESUMO
Strongyloides venezuelensis has been used in different experimental studies, such as those aimed at the evaluation of diagnostic techniques for human strongyloidiasis, mainly the molecular diagnosis. In this study, three regions (genus, 18S and 28S targets) of Strongyloides ribosomal DNA were evaluated for the molecular diagnosis of experimental strongyloidiasis. Rats were infected subcutaneously with 400 or 4000 S. venezuelensis infective larvae (400iL3 and 4000iL3), and kept for 35 days. Fecal samples were collected daily to count eggs per gram of feces (EPG) and to perform the polymerase chain reaction (PCR). Egg count started on the 5th day post-infection (pi) and ended on days 33 and 34 pi, in 400iL3 and 4000iL3 groups, respectively. Based in EPG, fecal samples were selected from days 2, 5, 8, 11, 15, 23 and 35 pi for DNA extraction; PCR (genus, 18S and 28S); and sequencing. The PCR-28S products showed higher values of identity (95-100%) in the database with the Strongyloides sequences. Therefore, it is possible to reinforce the application of PCR-28S in the diagnosis of experimental and human strongyloidiasis.
Assuntos
DNA Ribossômico/genética , RNA Ribossômico 18S/genética , RNA Ribossômico 28S/genética , Strongyloides/genética , Estrongiloidíase/diagnóstico , Animais , DNA de Helmintos/genética , DNA de Helmintos/isolamento & purificação , DNA Ribossômico/isolamento & purificação , Fezes/parasitologia , Humanos , Larva/genética , Masculino , Contagem de Ovos de Parasitas , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Strongyloides/patogenicidadeRESUMO
Parasitic helminths can reside in humans owing to their ability to disrupt host protective immunity. Receptor for advanced glycation end products (RAGE), which is highly expressed in host skin, mediates inflammatory responses by regulating the expression of pro-inflammatory cytokines and endothelial adhesion molecules. In this study, we evaluated the effects of venestatin, an EF-hand Ca2+-binding protein secreted by the parasitic helminth Strongyloides venezuelensis, on RAGE activity and immune responses. Our results demonstrated that venestatin bound to RAGE and downregulated the host immune response. Recombinant venestatin predominantly bound to the RAGE C1 domain in a Ca2+-dependent manner. Recombinant venestatin effectively alleviated RAGE-mediated inflammation, including footpad edema in mice, and pneumonia induced by an exogenous RAGE ligand. Infection experiments using S. venezuelensis larvae and venestatin silencing via RNA interference revealed that endogenous venestatin promoted larval migration from the skin to the lungs in a RAGE-dependent manner. Moreover, endogenous venestatin suppressed macrophage and neutrophil accumulation around larvae. Although the invasion of larvae upregulated the abundance of RAGE ligands in host skin tissues, mRNA expression levels of tumor necrosis factor-α, cyclooxygenase-2, endothelial adhesion molecules vascular cell adhesion protein-1, intracellular adhesion molecule-1, and E-selectin were suppressed by endogenous venestatin. Taken together, our results indicate that venestatin suppressed RAGE-mediated immune responses in host skin induced by helminthic infection, thereby promoting larval migration. The anti-inflammatory mechanism of venestatin may be targeted for the development of anthelminthics and immunosuppressive agents for the treatment of RAGE-mediated inflammatory diseases.
Assuntos
Proteínas de Helminto/metabolismo , Interações Hospedeiro-Parasita/fisiologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Strongyloides/imunologia , Strongyloides/metabolismo , Estrongiloidíase/metabolismo , Animais , Larva/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Strongyloides/patogenicidadeRESUMO
OBJECTIVE: To evaluate the dynamics of S. venezuelensis infection in Wistar rats of different age ranges. DESIGN: Thirty-five (n = 35, 7 per group) male Wistar rats were distributed according to age into five groups: 2, 3, 6, 12 and 18 months old (mo). The rats were infected by S. venezuelensis and eggs per gram of feces (EPG) were measured at 3, 9, 15 and 21 days post-infection (dpi). All animals were killed at 21 dpi, thymus, lungs and small intestines were removed, and relative weight calculated. The adult worms recovered from the small intestines and blood cells were counted. RESULTS: Rats in advanced age presented higher parasite oviposition at 9 dpi and posterior reduction of EPG, while young rats still showed higher oviposition at 15 dpi and 21 dpi. At 12 and 18 mo, the rats had greater number of adult worms, which with low fecundity, eosinophilia and least concentration of monocytes. The fecundity of worms was more expressive in young rats. A strong correlation was observed between age and EPG at 9 dpi (R = 0.72, p < 0.0001), at 15 (R = -0.66, p < 0.0001) and at 21 dpi (R = -0.65, p < 0.0001), as well as age and numbers of worms at 21 dpi (R = 0.74, p < 0.0001). The relative weight of the thymus, lungs and small intestines were higher in rats at 2 and 3 mo in comparison to the older groups of rats. CONCLUSIONS: Aging process interfered on host-parasite relationship and changed the dynamics of infection of S. venezuelensis in Wistar rats.
Assuntos
Envelhecimento/fisiologia , Strongyloides/patogenicidade , Estrongiloidíase/fisiopatologia , Fatores Etários , Análise de Variância , Animais , Fezes/parasitologia , Feminino , Fertilidade , Gerbillinae/parasitologia , Interações Hospedeiro-Parasita , Intestino Delgado/parasitologia , Masculino , Contagem de Ovos de Parasitas , Ratos , Ratos Wistar , Strongyloides/fisiologia , Estrongiloidíase/epidemiologia , Estrongiloidíase/parasitologiaRESUMO
Human strongyloidiasis a soil-transmitted infection caused by Strongyloides stercoralis is one of the most neglected amongst the so-called Neglected Tropical Diseases (NTDs). S. stercoralis is a nematode, which is distributed worldwide; it has been estimated that it could affect millions of people, mainly in tropical and subtropical endemic regions. The difficulties of diagnosis lead to infection rates being underreported. Asymptomatic patients have chronic infections that can lead to severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. Strongyloidiasis can easily be misdiagnosed because conventional faecal-based techniques lack of sensitivity for the morphological identification of infective larvae in faeces. None of the currently used molecular methods have used urine samples as an alternative to faecal samples for diagnosing strongyloidiasis. This study was thus aimed at comparing, for the first time, the use of a new loop-mediated isothermal amplification (LAMP) molecular assay (Strong-LAMP) to traditional methods on patients' urine samples. Twenty-four urine samples were taken from patients included in a study involving two Spanish hospitals for strongyloidiasis screening using parasitological and serological tests. Strongyloides larvae were found in 11 patients' faecal samples, thereby ascertaining that they had the disease. Other patients had high antibody titres but no larvae were found in their faeces. All urine samples were analysed by PCR and Strong-LAMP assay. No amplification occurred when using PCR. Strong-LAMP led to detecting S. stercoralis DNA in urine samples from patients having previously confirmed strongyloidiasis by parasitological tests and/or a suspicion of being infected by serological ones. The Strong-LAMP assay is a useful molecular tool for research regarding strongyloidiasis in human urine samples. After further validation, the Strong-LAMP assay could also be used for complementary and effective diagnosis of strongyloidiasis in a clinical setting.
Assuntos
Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Strongyloides/genética , Estrongiloidíase/diagnóstico , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificação de Ácido Nucleico/normas , RNA Ribossômico 18S/genética , Sensibilidade e Especificidade , Strongyloides/isolamento & purificação , Strongyloides/patogenicidade , Estrongiloidíase/microbiologia , Estrongiloidíase/urinaRESUMO
The present study is aimed at evaluating serological method using scFv anti-Strongyloides sp. and reporting the frequencies of the results with conventional parasitological technique (faeces) in elderly individuals. Among 112 elderly individuals (≥60 years of age), 14.28% were positive for at least one enteroparasite, with one individual positive for S. stercoralis. Sera were evaluated for the presence of anti-Strongyloides sp. antibodies using total or detergent fraction extracts of Strongyloides venezuelensis, which presented positivity rates of 19.64% and 10.71%, respectively. An anti-HSP60 single-chain variable fragment from Strongyloides sp. was used to detect parasite antigens, with 5.36% (6 individuals) of ELISA-positive individuals returning a positive result. While the serological test indicates previous or recent infection and may be limited by antigen purification, the anti-HSP60 method reflects the presence of Strongyloides sp. immune complexes and exhibits greater sensitivity and specificity. Our results demonstrate the variable occurrence of enteroparasites in elderly individuals residing in long-term nursing homes and validate a novel epidemiological tool to describe infection cases by Strongyloides sp.
Assuntos
Anticorpos Anti-Helmínticos/sangue , Complexo Antígeno-Anticorpo/sangue , Antígenos de Helmintos/sangue , Chaperonina 60/sangue , Anticorpos de Cadeia Única/sangue , Estrongiloidíase/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Brasil , Chaperonina 60/imunologia , Fezes/parasitologia , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Pessoa de Meia-Idade , Casas de Saúde , Sensibilidade e Especificidade , Anticorpos de Cadeia Única/imunologia , Strongyloides/crescimento & desenvolvimento , Strongyloides/imunologia , Strongyloides/patogenicidade , Estrongiloidíase/sangue , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologiaRESUMO
Gastrointestinal parasites colonizing the mammalian gut influence the host immune system and health. Parasite infections, mainly helminths, have been studied intensively in both humans and non-human animals, but relatively rarely within a conservation framework. The Udzungwa red colobus monkey (Procolobus gordonorum) is an endangered endemic primate species living in the Udzungwa Mountains of Tanzania, a global biodiversity hotspot. Since this endemic primate species is highly sensitive to human disturbance, here we investigate whether habitat type (driven by natural and human-induced factors) is associated with helminth diversity. Using standard flotation and sedimentation techniques, we analyzed 251 fecal samples belonging to 25 social groups from four different forest blocks within the Udzungwa Mountains. Five parasitic helminth taxa were recovered from Udzungwa red colobus, including Trichuris sp., Strongyloides fulleborni, S. stercoralis, a strongylid nematode and Colobenterobius sp. We used Generalized Linear Mixed Models to explore the contribution of habitat type, altitude and fecal glucocorticoid levels (as biomarkers of stress) in predicting gut parasite variation. Although some parasites (e.g., Trichuris sp.) infected more than 50% of individuals, compared to others (e.g., Colobenterobius sp.) that infected less than 3%, both parasite richness and prevalence did not differ significantly across forests, even when controlling for seasonality. Stress hormone levels also did not predict variation in parasite richness, while altitude could explain it resulting in lower richness at lower altitudes. Because human activities causing disturbance are concentrated mainly at lower altitudes, we suggest that protection of primate forest habitat preserves natural diversity at both macro- and microscales, and that the importance of the latter should not be underestimated.
Assuntos
Altitude , Colobinae/parasitologia , Ecossistema , Estresse Psicológico/parasitologia , Animais , Colobinae/fisiologia , Espécies em Perigo de Extinção , Strongyloides/patogenicidade , Trichuris/patogenicidadeRESUMO
Soil-transmitted helminths (STHs) are medically important parasites that infect 1. 5 billion humans globally, causing a substantial disease burden. These parasites infect the gastrointestinal tract (GIT) of their host where they co-exist and interact with the host gut bacterial flora, leading to the coevolution of the parasites, microbiota, and host organisms. However, little is known about how these interactions change through time with the progression of infection. Strongyloidiasis is a human parasitic disease caused by the nematode Strongyloides stercoralis infecting 30-100 million people. In this study, we used a closely related rodent parasite Strongyloides venezuelensis and mice as a model of gastrointestinal parasite infection. We conducted a time-course experiment to examine changes in the fecal microbiota from the start of infection to parasite clearance. We found that bacterial taxa in the host intestinal microbiota changed significantly as the infection progressed, with an increase in the genera Bacteroides and Candidatus Arthromitus, and a decrease in Prevotella and Rikenellaceae. However, the microbiota recovered to the pre-infective state after parasite clearance from the host, suggesting that these perturbations are reversible. Microarray analysis revealed that this microbiota transition is likely to correspond with the host immune response. These findings give us an insight into the dynamics of parasite-microbiota interactions in the host gut during parasite infection.
Assuntos
Bactérias/classificação , Microbioma Gastrointestinal/fisiologia , Intestinos/microbiologia , Intestinos/parasitologia , Strongyloides/fisiologia , Estrongiloidíase/microbiologia , Estrongiloidíase/parasitologia , Animais , Bactérias/genética , Biodiversidade , Modelos Animais de Doenças , Fezes/microbiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Interações Hospedeiro-Parasita/imunologia , Interações Hospedeiro-Parasita/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nematoides , Parasitos , RNA Ribossômico 16S/genética , Strongyloides/patogenicidadeRESUMO
Parenteral ivermectin treatment of disseminated strongyloidiasis and hyperinfection is increasing, although not licensed in humans and with limited pharmacokinetic data available. Plasma and postmortem tissue analysis in an human immunodeficiency virus (HIV)/hepatitis C virus-positive man with disseminated strongyloidiasis suggests loading subcutaneous ivermectin doses are required, from which the central nervous system is protected.
Assuntos
Antiparasitários/farmacocinética , Diarreia/diagnóstico , Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Pseudo-Obstrução Intestinal/diagnóstico , Ivermectina/farmacocinética , Estrongiloidíase/diagnóstico , Adulto , Animais , Autopsia , Diarreia/complicações , Diarreia/tratamento farmacológico , Diarreia/patologia , Evolução Fatal , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Humanos , Injeções Subcutâneas , Pseudo-Obstrução Intestinal/complicações , Pseudo-Obstrução Intestinal/tratamento farmacológico , Pseudo-Obstrução Intestinal/patologia , Masculino , Strongyloides/patogenicidade , Strongyloides/fisiologia , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/patologiaRESUMO
Strongyloides spp., gastrointestinal nematode parasites of humans and other animals, have genetically identical parasitic and free-living adult life cycle stages. This is an almost unique feature amongst nematodes and comparison of these two stages can provide insights into the genetic basis and evolution of Strongyloides nematode parasitism. Here, we present RNAseq data for S. venezuelensis, a parasite of rodents, and identify genes that are differentially expressed in parasitic and free-living life cycle stages. Comparison of these data with analogous RNAseq data for three other Strongyloides spp., has identified key protein-coding gene families with a putative role in parasitism including WAGO-like Argonautes (at the genus level) and speckle-type POZ-like coding genes (S. venezuelensis-S. papillosus phylogenetic subclade level). Diverse gene families are uniquely upregulated in the parasitic stage of all four Strongyloides species, including a distinct upregulation of genes encoding cytochrome P450 in S. venezuelensis, suggesting some diversification of the molecular tools used in the parasitic life cycle stage among individual species. Together, our results identify key gene families with a putative role in Strongyloides parasitism or features of the parasitic life cycle stage, and deepen our understanding of parasitism evolution among Strongyloides species.
Assuntos
Filogenia , Strongyloides/genética , Estrongiloidíase/genética , Transcriptoma/genética , Animais , Proteínas de Helminto/classificação , Proteínas de Helminto/genética , Humanos , Larva/genética , Larva/patogenicidade , Estágios do Ciclo de Vida/genética , Ratos Wistar , Roedores/parasitologia , Strongyloides/patogenicidade , Estrongiloidíase/parasitologia , Simbiose/genéticaAssuntos
Antinematódeos/uso terapêutico , Antiplatelmínticos/uso terapêutico , Seleção do Doador/métodos , Transplante de Órgãos/métodos , Schistosoma/efeitos dos fármacos , Esquistossomose/tratamento farmacológico , Strongyloides/efeitos dos fármacos , Estrongiloidíase/tratamento farmacológico , Doadores de Tecidos , Transplantados , Animais , Antinematódeos/efeitos adversos , Antiplatelmínticos/efeitos adversos , Seleção do Doador/normas , Interações Hospedeiro-Parasita , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/normas , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco , Schistosoma/isolamento & purificação , Schistosoma/patogenicidade , Esquistossomose/diagnóstico , Esquistossomose/parasitologia , Esquistossomose/transmissão , Strongyloides/isolamento & purificação , Strongyloides/patogenicidade , Estrongiloidíase/diagnóstico , Estrongiloidíase/parasitologia , Estrongiloidíase/transmissão , Resultado do TratamentoRESUMO
BACKGROUND: Human strongyloidiasis is a chronic and persistent gastrointestinal disease caused by infection with soil-transmitted helminths of the genus Strongyloides. The aim of this research was to obtain diagnostic prevalence regarding strongyloidiasis in northeast Thailand through a hospital-based study. METHODS: Patients' demographic data and the results of stool examinations conducted using the formalin ethyl acetate concentration technique were collected from the parasitology laboratory records at Srinagarind Hospital in Khon Kaen, Thailand. The relevant information from years 2004 to 2014 was collected and descriptively analyzed. RESULTS: Of a total of 22,338 patients, 3889 (17.4%) had stool samples that tested positive for Strongyloides larvae. The highest prevalence was 22.8% (95% CI = 19.6-26.2%) in the year 2004. This percentage progressively decreased, reaching 11.2% (95% CI = 10.2-12.4%) in 2013 and remaining stable at 12.9% (95% CI = 11.8-14.1%) in 2014. Males (2741 cases) had double the positivity rate of females (1148 cases). The prevalence of infection was highest (25.9%; 95% CI = 24.5-27.3%) among patients that were 51-60 years of age. CONCLUSIONS: Areas endemic for strongyloidiasis should be emphasized under the national helminth control program and health education campaigns. Nationwide assessments should also be performed regarding Strongyloides infection, including risk factors, treatment, and prevention. The diagnostic laboratory data presented here identify the geographical focus of disease to be the northeastern region of the country. Further targeted surveillance using more sensitive methods will almost certainly reveal a higher individual disease burden than found in this report.
Assuntos
Estrongiloidíase/epidemiologia , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Feminino , Hospitais , Humanos , Larva , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Strongyloides/patogenicidade , Estrongiloidíase/diagnóstico , Tailândia/epidemiologia , Adulto JovemRESUMO
The majority of the 30-100 million people infected with Strongyloides stercoralis, a soil transmitted intestinal nematode, have subclinical (or asymptomatic) infections. These infections are commonly chronic and longstanding because of the autoinfective process associated with its unique life cycle. A change in immune status can increase parasite numbers, leading to hyperinfection syndrome, dissemination, and death if unrecognized. Corticosteroid use and HTLV-1 infection are most commonly associated with the hyperinfection syndrome. Strongyloides adult parasites reside in the small intestine and induce immune responses both local and systemic that remain poorly characterized. Definitive diagnosis of S. stercoralis infection is based on stool examinations for larvae, but newer diagnostics - including new immunoassays and molecular tests - will assume primacy in the next few years. Although good treatment options exist for infection and control of this infection might be possible, S. stercoralis remains largely neglected.
Assuntos
Strongyloides/classificação , Strongyloides/patogenicidade , Estrongiloidíase/patologia , Estrongiloidíase/parasitologia , Animais , Anti-Helmínticos/uso terapêutico , Testes Diagnósticos de Rotina , Humanos , Técnicas de Diagnóstico Molecular/métodos , Parasitologia/métodos , Prevalência , Strongyloides/imunologia , Estrongiloidíase/diagnóstico , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/epidemiologiaRESUMO
Parasitic nematodes are important and abundant parasites adapted to live a parasitic lifestyle, with these adaptations all aimed at facilitating their survival and reproduction in their hosts. The recently sequenced genomes of four Strongyloides species, gastrointestinal parasites of humans and other animals, alongside transcriptomic and proteomic analysis of free-living and parasitic stages of their life cycles have revealed a number of protein families with a putative role in their parasitism. Many of these protein families have also been associated with parasitism in other parasitic nematode species, suggesting that these proteins may play a fundamental role in nematode parasitism more generally. Here, we review key protein families that have a putative role in Strongyloides' parasitism - acetylcholinesterases, astacins, aspartic proteases, prolyl oligopeptidases, proteinase inhibitors (trypsin inhibitors and cystatins), SCP/TAPS and transthyretin-like proteins - and the evidence for their key, yet diverse, roles in the parasitic lifestyle.
Assuntos
Proteínas de Helminto/genética , Interações Hospedeiro-Parasita , Strongyloides/genética , Fatores de Virulência/genética , Animais , Humanos , Strongyloides/patogenicidade , Estrongiloidíase/parasitologiaRESUMO
Strongyloides spp. are common parasites of vertebrates and two species, S. ratti and S. venezuelensis, parasitize rats; there are no known species that naturally infect mice. Strongyloides ratti and S. venezuelensis overlap in their geographical range and in these regions co-infections appear to be common. These species have been widely used as tractable laboratory systems in rats as well as mice. The core biology of these two species is similar, but there are clear differences in aspects of their within-host biology as well as in their free-living generation. Phylogenetic evidence suggests that S. ratti and S. venezuelensis are the result of two independent evolutionary transitions to parasitism of rats, which therefore presents an ideal opportunity to begin to investigate the basis of host specificity in Strongyloides spp.
Assuntos
Modelos Animais de Doenças , Doenças dos Roedores/patologia , Doenças dos Roedores/parasitologia , Strongyloides/crescimento & desenvolvimento , Strongyloides/patogenicidade , Estrongiloidíase/patologia , Estrongiloidíase/parasitologia , Animais , Especificidade de Hospedeiro , Camundongos , Ratos , Strongyloides/fisiologia , Fatores de VirulênciaRESUMO
The human pathogenic nematode Strongyloides stercoralis infects approximately 30-100 million people worldwide. Analysis of the adaptive immune response to S. stercoralis beyond descriptive studies is challenging, as no murine model for the complete infection cycle is available. However, the combined employment of different models each capable of modelling some features of S. stercoralis life cycle and pathology has advanced our understanding of the immunological mechanisms involved in host defence. Here we review: (i) studies using S. stercoralis third stage larvae implanted in diffusion chambers in the subcutaneous tissue of mice that allow analysis of the immune response to the human pathogenic Strongyloides species; (ii) studies using Strongyloides ratti and Strongyloides venezuelensis that infect mice and rats to extend the analysis to the parasites intestinal life stage and (iii) studies using S. stercoralis infected gerbils to analyse the hyperinfection syndrome, a severe complication of human strongyloidiasis that is not induced by rodent specific Strongyloides spp. We provide an overview of the information accumulated so far showing that Strongyloides spp. elicits a classical Th2 response that culminates in different, site specific, effector functions leading to either entrapment and killing of larvae in the tissues or expulsion of parasitic adults from the intestine.
Assuntos
Imunidade Adaptativa , Doenças dos Roedores/imunologia , Strongyloides/imunologia , Strongyloides/patogenicidade , Estrongiloidíase/veterinária , Animais , Camundongos , Ratos , Doenças dos Roedores/parasitologia , Estrongiloidíase/imunologia , Estrongiloidíase/parasitologia , Células Th2/imunologiaRESUMO
Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism.
Assuntos
Genômica , Strongyloides/genética , Estrongiloidíase/genética , Simbiose/genética , Animais , Evolução Biológica , Humanos , Estágios do Ciclo de Vida/genética , Strongyloides/patogenicidade , Estrongiloidíase/parasitologia , Transcriptoma/genéticaRESUMO
Strongyloidiasis is an intestinal parasitosis with an obligatory pulmonary cycle. A Th2-type immune response is induced and amplifies the cellular response through the secretion of inflammatory mediators. Although this response has been described as being similar to asthma, airway remodeling during pulmonary migration of larvae has not yet been established. The aim of this study was to identify the occurrence of airway remodeling during Strongyloides venezuelensis (S. v.) infection and to determine the ability of dexamethasone treatment to interfere with the mechanisms involved in this process. Rats were inoculated with 9,000 S. v. larvae, treated with dexamethasone (2 mg/kg) and killed at 1, 3, 5, 7, 14 and 21 days. Morphological and morphometric analyzes with routine stains and immunohistochemistry were conducted, and some inflammatory mediators were evaluated using ELISA. Goblet cell hyperplasia and increased bronchiolar thickness, characterized by edema, neovascularization, inflammatory infiltrate, collagen deposition and enlargement of the smooth muscle cell layer were observed. VEGF, IL1-ß and IL-4 levels were elevated throughout the course of the infection. The morphological findings and the immunomodulatory response to the infection were drastically reduced in dexamethasone-treated rats. The pulmonary migration of S. venezuelensis larvae produced a transitory, but significant amount of airway remodeling with a slight residual bronchiolar fibrosis. The exact mechanisms involved in this process require further study.
Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Dexametasona/farmacologia , Pulmão/parasitologia , Strongyloides/patogenicidade , Estrongiloidíase/fisiopatologia , Traqueia/efeitos dos fármacos , Animais , Brônquios/fisiopatologia , Interleucina-1beta/sangue , Interleucina-4/sangue , Larva/crescimento & desenvolvimento , Larva/patogenicidade , Masculino , Miócitos de Músculo Liso , Ratos , Ratos Wistar , Strongyloides/crescimento & desenvolvimento , Estrongiloidíase/parasitologia , Traqueia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The aim of this study was to investigate the immunomodulatory effects of glucocorticoids on the immune response to Strongyloides venezuelensis in mice. Balb/c mice were infected with S. venezuelensis and treated with Dexamethasone (Dexa) or vehicle. Dexa treatment increased circulating blood neutrophil numbers and inhibited eosinophil and mononuclear cell accumulation in the blood, bronchoalveolar, and peritoneal fluid compared with control animals. Moreover, Dexa decreased tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-3 (IL-3), IL-4, IL-5, IL-10, and IL-12 production in the lungs and circulating immunoglobulin G1 (IgG1), IgG2a, and IgE antibody levels while increasing the overall parasite burden in the feces and intestine. Dexa treatment enhanced the fertility of female nematodes relative to untreated and infected mice. In summary, the alterations in the immune response induced by Dexa resulted in a blunted, aberrant immune response associated with increased parasite burden. This phenomenon is similar to that observed in S. stercoralis-infected humans who are taking immunosuppressive or antiinflammatory drugs, including corticosteroids.
Assuntos
Dexametasona/efeitos adversos , Fertilidade/efeitos dos fármacos , Strongyloides/efeitos dos fármacos , Estrongiloidíase/imunologia , Estrongiloidíase/patologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/imunologia , Fezes/parasitologia , Feminino , Interações Hospedeiro-Parasita , Imunoglobulina G/sangue , Intestinos/imunologia , Intestinos/parasitologia , Intestinos/patologia , Leucócitos Mononucleares/imunologia , Pulmão/parasitologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Contagem de Ovos de Parasitas , Ratos , Ratos Wistar , Strongyloides/patogenicidadeRESUMO
According to the hygiene hypothesis, the increased incidence of allergic and autoimmune diseases in developed countries is mainly explained by the decreased contact between the human population and certain environmental agents as lactobacillus, mycobacteria and helminths. In this study, we evaluated the effect of multiple infections with Strongyloides venezuelensis on the development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Multiple infections before EAE induction were not able to change the evolution of the disease. No alterations were observed in weight loss, clinical score and inflammation intensity at the central nervous system. The presence of significant levels of parasite-specific IgG1 but not IgG2b suggested a Th2 polarization. However, the percentage and absolute number of CD4+CD25+Foxp3+ T cells were not changed, being their levels in the spleen and lymph nodes of infected rats comparable to the ones found in normal animals. These results suggest that a Th2-polarized response without concomitant expansion of Foxp3+ regulatory T cells was not able to modify EAE progression. Even though these results do not threaten the hygiene hypothesis, they suggest that this paradigm might be an oversimplification. They also emphasize the need of a study to compare the immunoregulatory ability associated with different helminth spp.
Assuntos
Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/patologia , Strongyloides/patogenicidade , Estrongiloidíase/complicações , Estrongiloidíase/patologia , Animais , Anticorpos Anti-Helmínticos/sangue , Peso Corporal , Antígenos CD4/análise , Sistema Nervoso Central/patologia , Feminino , Fatores de Transcrição Forkhead/análise , Imunoglobulina G/sangue , Subunidade alfa de Receptor de Interleucina-2/análise , Ratos , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/imunologia , Células Th2/imunologiaRESUMO
Notch receptor-mediated signaling is involved in the developmental process and functional modulation of lymphocytes, as well as in mast cell differentiation. Here, we investigated whether Notch signaling is required for antipathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice but accumulated abnormally in the lamina propria of the small-intestinal mucosa of the Notch2-conditional knockout mice in naive status. When transplanted into mast cell-deficient W(sh)/W(sh) mice, Notch2-null bone marrow-derived mast cells were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control bone marrow-derived mast cells were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 larvae of Strongyloides venezuelensis, the abundant number of mast cells was rapidly mobilized to the epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2-conditional knockout mice, accompanied by impaired eradication of Strongyloides venezuelensis. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells and further imply a critical role of Notch signaling in the host-pathogen interface in the small intestine.