RESUMEN
Following our previous findings on the in vitro anthelmintic effect of camel milk on Haemonchus contortus, the current study aimed at investigating its in vivo effect. Investigations were carried out using mice infected with Heligmosomoides polygyrus which is a parasite commonly used to test the efficacy of anthelmintics. Thirty six Swiss white mice of both sexes aged 5 - 6 weeks old, and weighing between 20 and 25 g were orally infected with 0.5 ml dose of 100, 1-week-old H. polygyrus infective larvae (L3). After the pre-patent period, infected animals were randomly divided into 6 groups of 6 animals each. The nematicidal efficacy of camel milk was monitored through faecal egg count reduction (FECR) and total worm count reduction (TWCR). Four doses (8.25; 16.5; 33.0; 66.0 ml/kg body weight (bw)) for fresh camel milk and 22 mg/kg bw for albendazole were studied using a bioassay. Albendazole and 4 % dimethylsulfoxide were included in the protocol as reference drug and placebo, respectively. For all tested doses except 8.25 ml/kg bw, camel milk was effective in vivo against H. polygyrus reducing both faecal egg count and worm count (p < 0.05). The dose 66 ml/kg bw showed the highest nematicidal activity causing a 76.75 % FECR and a 69.62 % TWCR 7 day after initiating the treatment. These results support the possible use of camel milk in the control of gastro-intestinal helminthiasis.
RESUMEN
There is increasing recognition that exposures to infectious agents evoke fundamental effects on the development and behaviour of the immune system. Moreover, where infections (especially parasitic infections) have declined, immune responses appear to be increasingly prone to hyperactivity. For example, epidemiological studies of parasite-endemic areas indicate that prenatal or early-life experience of infections can imprint an individual's immunological reactivity. However, the ability of helminths to dampen pathology in established inflammatory diseases implies that they can have therapeutic effects even if the immune system has developed in a low-infection setting. With recent investigations of how parasites are able to modulate host immune pathology at the level of individual parasite molecules and host cell populations, we are now able to dissect the nature of the host-parasite interaction at both the initiation and recall phases of the immune response. Thus the question remains - is the influence of parasites on immunity one that acts primarily in early life, and at initiation of the immune response, or in adulthood and when recall responses occur? In short, parasite immunosuppression - sooner or later?
Asunto(s)
Enfermedades Autoinmunes/terapia , Helmintiasis/inmunología , Helmintos/inmunología , Hipótesis de la Higiene , Terapia de Inmunosupresión , Inmunoterapia/métodos , Terapia con Helmintos , Animales , Enfermedades Autoinmunes/inmunología , Interacciones Huésped-Parásitos , Humanos , Sistema Inmunológico , Inmunoterapia/tendenciasRESUMEN
Schistosoma haematobium antigen recognition profiles of the human isotypes IgA, IgE, IgG1 and IgG4 were compared by image analysis of western blots. Adult worm antigens separated by two-dimensional gel electrophoresis were probed with pooled sera from Zimbabweans resident in a S. haematobium endemic area, followed by the identification of individual antigenic parasite proteins using mass spectrometry. Overall, IgG1 reacted with the largest number of antigens, followed by IgE and IgA which detected the same number, while IgG4 detected the fewest antigens. IgE recognized all antigens reactive with IgG4 as well as an additional four antigens, an isoform of 28-kDa GST, phosphoglycerate kinase, actin 1 and calreticulin. IgG1 additionally recognized fatty acid-binding protein, triose-phosphate isomerase and heat shock protein 70, which were not recognized by IgA. Recognition patterns varied between some isoforms, e.g. the two fructose 1-6-bis-phosphate aldolase isoforms were differentially recognized by IgA and IgG1. Although the majority of S. haematobium adult worm antigens are recognized by all of the four isotypes, there are clear restrictions in antibody recognition for some antigens. This may partly explain differences observed in isotype dynamics at a population level. Differential recognition patterns for some isoforms indicated in the study have potential importance for vaccine development.
Asunto(s)
Anticuerpos Antihelmínticos/sangre , Inmunoglobulina A/sangre , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Schistosoma haematobium/inmunología , Animales , Antígenos Helmínticos/inmunología , Western Blotting , Electroforesis en Gel Bidimensional , Humanos , Procesamiento de Imagen Asistido por Computador , Espectrometría de Masas , Proteoma/inmunologíaRESUMEN
Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The 'trade-off' between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.
Asunto(s)
Helmintiasis/inmunología , Helmintos/inmunología , Interacciones Huésped-Parásitos/inmunología , Animales , Antígenos Helmínticos/inmunología , Evolución Biológica , Femenino , Heterogeneidad Genética , Helmintiasis/epidemiología , Helmintiasis/genética , Helmintiasis/parasitología , Helmintos/genética , Interacciones Huésped-Parásitos/genética , Humanos , Inmunidad Celular , Inmunidad Humoral , Estadios del Ciclo de Vida/inmunología , Masculino , RatonesRESUMEN
Regulatory T cells play a crucial role in normal gut homeostasis, as well as during infection with microbial or parasitic pathogens. Prior to infection, interactions with the commensal microflora are essential to differentiation of a healthy steady-state level of immunoregulation, mediated through both Toll-like receptor-dependent and -independent pathways. The ingress of pathogenic organisms may, according to the context, promote or reverse the regulatory environment, with onward consequences for inflammation in both the intestinal and extra-intestinal settings. Appropriate regulation of gut immunity thus depends upon a complex three-way interplay between host cells, commensals and pathogens, and can exert a major impact on systemic responses including allergy and autoimmunity.
Asunto(s)
Enfermedades Transmisibles/inmunología , Inflamación/inmunología , Intestinos/inmunología , Linfocitos T Reguladores/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/microbiología , Enfermedad Crónica , Homeostasis/inmunología , Interacciones Huésped-Parásitos/inmunología , Humanos , Intestinos/microbiología , Enfermedades Parasitarias/inmunología , Receptores Toll-Like/inmunologíaRESUMEN
A macrophage migration inhibitory factor (MIF)-like molecule, Tci-MIF-1, was isolated from Teladorsagia circumcincta and subjected to detailed characterization. A cDNA representing Tci-mif-1 was isolated following its identification in third-stage larvae (L3)-enriched cDNA population. Sequencing of the cDNA indicated a 348-bp open reading frame (ORF) with the closest orthologue being a MIF derived from the human hookworm Ancylostoma ceylanicum. Messenger RNA (mRNA) representing the Tci-MIF-1 transcript was detected in eggs, L3 and adult stages of T. circumcincta. The transcript was also present, but to a lesser extent in fourth-stage larvae (L4). Detection of Tci-MIF-1 protein in T. circumcincta developmental stages reflected the transcript levels identified by reverse transcriptase-PCR. Using immunohistochemistry, the Tci-MIF-1 protein was shown to have a diffuse distribution in L3 tissue, and in L4 and adult stages, the protein was localized to the nematode gut. A recombinant version of Tci-MIF-1 was produced, and enzymic assays indicated that this recombinant protein and a somatic extract of L3 possessed dopachrome tautomerase activity as has been observed previously in other MIF-like molecules. Neither native, purified Tci-MIF nor recombinant Tci-MIF-1 dramatically influenced the in vitro migration of sheep monocytes.
Asunto(s)
Movimiento Celular , Proteínas del Helminto/inmunología , Tolerancia Inmunológica , Oxidorreductasas Intramoleculares/inmunología , Macrófagos/inmunología , Trichostrongyloidea/enzimología , Trichostrongyloidea/inmunología , Secuencia de Aminoácidos , Animales , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , ADN de Helmintos/genética , ADN de Helmintos/aislamiento & purificación , Tracto Gastrointestinal/química , Perfilación de la Expresión Génica , Proteínas del Helminto/análisis , Humanos , Inmunohistoquímica , Oxidorreductasas Intramoleculares/análisis , Larva/química , Macrófagos/parasitología , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Ovinos , Trichostrongyloidea/químicaRESUMEN
The transforming growth factor-beta (TGF-beta) gene family regulates critical processes in animal development, and plays a crucial role in regulating the mammalian immune response. We aimed to identify TGF-beta homologues from 2 laboratory model nematodes (Heligmosomoides polygyrus and Nippostrongylus brasiliensis) and 2 major parasites of ruminant livestock (Haemonchus contortus and Teladorsagia circumcincta). Parasite cDNA was used as a template for gene-specific PCR and RACE. Homologues of the TGH-2 subfamily were isolated, and found to differ in length (301, 152, 349 and 305 amino acids respectively), with variably truncated N-terminal pre-proteins. All contained conserved C-terminal active domains (>85% identical over 115 amino acids) containing 9 cysteine residues, as in C. elegans DAF-7, Brugia malayi TGH-2 and mammalian TGF-beta. Surprisingly, only the H. contortus homologue retained a conventional signal sequence, absent from shorter proteins of other species. RT-PCR assays of transcription showed that in H. contortus and N. brasiliensis expression was maximal in the infective larval stage, and very low in adult worms. In contrast, in H. polygyrus and T. circumcincta, tgh-2 transcription is higher in adults than infective larvae. The molecular evolution of this gene family in parasitic nematodes has diversified the pre-protein and life-cycle expression patterns of TGF-beta homologues while conserving the structure of the active domain.
Asunto(s)
Proteínas de Caenorhabditis elegans , Regulación del Desarrollo de la Expresión Génica , Proteínas del Helminto/metabolismo , Estadios del Ciclo de Vida , Homología de Secuencia de Aminoácido , Factor de Crecimiento Transformador beta , Trichostrongyloidea/crecimiento & desarrollo , Secuencia de Aminoácidos , Animales , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Perfilación de la Expresión Génica , Proteínas del Helminto/química , Proteínas del Helminto/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Nematospiroides dubius , Filogenia , Alineación de Secuencia , Factor de Crecimiento Transformador beta/química , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Trichostrongyloidea/clasificación , Trichostrongyloidea/genética , Trichostrongyloidea/metabolismoRESUMEN
Mammalian chitinase and chitinase-like proteins (CLPs) are a family of mediators increasingly associated with infection, T cell-mediated inflammation, wound healing, allergy and asthma. Although our current knowledge of the function of mammalian chitinases and CLPs is very limited, important information can be deduced from research carried out in lower organisms, and in different immunopathological conditions. Enzymatically active mammalian chitinase proteins may have evolved to degrade the copious amounts of chitin mammals are exposed to on a daily basis, and to form an innate barrier to chitin-containing organisms. CLPs are homologous to chitinases but lack the ability to degrade chitin. It is most striking that both chitinases and CLPs are up-regulated in T-helper type 2 (Th2)-driven conditions, and the first evidence is now emerging that these proteins may accentuate Th2 reactivity, and possibly contribute to the repair process that follows inflammation. Following studies demonstrating that chitinase inhibition leads to an attenuated allergic response, several strategies are being used to develop enzyme inhibitors for therapeutic use in human diseases. In this review, we will summarize recent insights into the effects of chitinases and CLPs in the context of Th2-dominated pathology with particular focus on allergy and asthma, discussing whether chitinase enzyme inhibitors may be of therapeutic value.
Asunto(s)
Quitinasas/antagonistas & inhibidores , Inhibidores Enzimáticos/uso terapéutico , Hipersensibilidad/tratamiento farmacológico , Células Th2/enzimología , Células Th2/inmunología , Animales , Asma/tratamiento farmacológico , Asma/enzimología , Asma/inmunología , Quitinasas/inmunología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Humanos , Hipersensibilidad/enzimología , Hipersensibilidad/inmunologíaRESUMEN
Helminth immunology is a field which has changed beyond recognition in the past 30 years, transformed not only by new technologies from cDNA cloning to flow cytometry, but also conceptually as our definition of host immune pathways has matured. The molecular revolution defined key nematode surface and secreted antigens, and identified candidate immunomodulators that are likely to underpin parasites' success in eluding immune attack. The immunological advances in defining cytokine networks, lymphocyte subsets and innate cell recognition have also made a huge impact on our understanding of helminth infections. Most recently, the ideas of regulatory immune cells, in particular the regulatory T cell, have again overturned older thinking, but also may explain immune hyporesponsiveness observed in chronic helminth diseases, as well as the link to reduced allergic reactions observed in human and animal infections. The review concludes with a forward look to where we may make future advances towards the final eradication of helminth diseases.
Asunto(s)
Antígenos de Superficie/inmunología , Helmintiasis/inmunología , Helmintiasis/patología , Helmintos/inmunología , Animales , Antígenos Helmínticos/inmunología , Helmintos/clasificación , Humanos/inmunología , Higiene , Hipersensibilidad/etiología , Hipersensibilidad/inmunologíaRESUMEN
Serine proteinase inhibitors are encoded by a large gene family of long evolutionary standing. Recent discoveries of parasite proteins that inhibit human serine proteinases, together with the complete genomic sequence from Caenorhabditis elegans, have provided a set of new serine proteinase inhibitors from more primitive metazoan animals such as nematodes. The structural features (e.g. reactive centre residues), gene organization (including intron arrangements) and inhibitory function and targets (e.g. inflammatory and coagulation pathway proteinase) all contribute important new insights into proteinase inhibitor evolution. Some parasite products have evolved that block enzymes in the mammalian host, but the human host responds with a significant immune response to the parasite inhibitors. Thus, infection produces a finely balanced conflict between host and pathogen at the molecular level, and this might have accelerated the evolution of these proteins in parasitic species as well as their hosts.
Asunto(s)
Nematodos/metabolismo , Serpinas/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Evolución Molecular , Datos de Secuencia Molecular , Nematodos/genética , Homología de Secuencia de Aminoácido , Serpinas/química , Serpinas/genética , Serpinas/metabolismoRESUMEN
Functional analysis of genes from parasitic helminths requires, at the present time, heterologous expression. We have adapted the well-characterized system of transfection in Leishmania protozoal parasites, as a means of analysing the effect of single filarial genes on the mammalian immune system. For example, testing the function of the Brugia malayi abundant larval transcript (ALT) gene-transfected Leishmania mexicana were found to be significantly more virulent in macrophages in vitro. The course of infection in vivo is also aggravated by expression of the ALT gene. Examples are also given of transgenes which reduced in vitro growth within macrophages, as well as others which exert no effect on the protozoal parasitism. Thus, Leishmania transfection provides a tractable system to analyse helminth gene function within the context of the host immune system.
Asunto(s)
Genes de Helminto , Helmintos/inmunología , Leishmania mexicana/genética , Biología Molecular/métodos , Animales , Helmintos/genética , TransfecciónRESUMEN
The present study aimed at analyzing the chemical composition and evaluating the in vitro and in vivo anthelmintic activity of Artemisia campestris essential oil aerial parts. The chemical composition was analysed by gaz chromatography/mass chromatography (GC/MS). Fifty compounds were identified representing 99.98% of the total oil. A. campestris essential oil was dominated by beta-pinene (36.40%) and 2-undecanone (14.7%). The in vitro anthelmintic activity tests of A. campestris essential oil were performed on Haemonchus contortus using egg hatch assay (EHA) and adult worm's motility assay (AWMA) compared with a reference drug albendazole. In the EHA 100% inhibition was observed at 2 mg/ml after 48 h incubation (IC50 = 0.93 mg/ml). In the AWMA, essential oil induced 66.6% inhibition at 0.5 mg/ml after 8 h post exposure. The nematicidal effect of essential oil was evaluated on Heligmosomoides polygyrus. It was monitored through faecal egg count reduction (FECR) and total worm count reduction (TWCR). Three doses (2000, 4000 and 5000 mg/kg) were studied using a bioassay. The dose of 5000 mg/kg showed a high nematicidal activity (72.1% FECR and 72% TWCR), 7 days post-treatment. The results of the present study suggest that A. campestris essential oil has a potential anthelmintic activity and further studies are required in order to establish its mechanisms of action.
Asunto(s)
Antihelmínticos/farmacología , Artemisia/química , Haemonchus/efectos de los fármacos , Aceites Volátiles/farmacología , Extractos Vegetales/análisis , Albendazol/farmacología , Animales , Antihelmínticos/química , Antihelmínticos/aislamiento & purificación , Heces/parasitología , Hemoncosis/tratamiento farmacológico , Hemoncosis/parasitología , Hemoncosis/veterinaria , Aceites Volátiles/análisis , Aceites Volátiles/química , Recuento de Huevos de Parásitos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ovinos , Enfermedades de las Ovejas/tratamiento farmacológicoRESUMEN
Helminth parasites induce strong immune responses that are initiated by cytokines, in the first instance interleukin-4 and interleukin-13. Recent studies of knockout mice deficient in these mediators or their shared receptor have revealed discrete pathways required for expulsion of different gut parasites.
Asunto(s)
Citocinas/inmunología , Parasitosis Intestinales/inmunología , Nematodos/inmunología , Infecciones por Nematodos/inmunología , Animales , Eosinófilos/inmunología , Mastocitos/inmunología , RatonesRESUMEN
While interference with the class I MHC pathway by pathogen-encoded gene products, especially those of viruses, has been well documented, few examples of specific interference with the MHC class II pathway have been reported. Potential targets for such interference are the proteases that remove the invariant chain chaperone and generate antigenic peptides. Indeed, recent studies indicate that immature dendritic cells express cystatin C to modulate cysteine protease activity and the expression of class II MHC molecules [1]. Here, we show that Bm-CPI-2, a recently discovered cystatin homolog produced by the filarial nematode parasite Brugia malayi (W. F. Gregory et al., submitted), inhibits multiple cysteine protease activities found in the endosomes/lysosomes of human B lymphocyte lines. CPI-2 blocked the hydrolysis of synthetic substrates favored by two different families of lysosomal cysteine proteases and blocked the in vitro processing of the tetanus toxin antigen by purified lysosome fractions. Moreover, CPI-2 substantially inhibited the presentation of selected T cell epitopes from tetanus toxin by living antigen-presenting cells. Our studies provide the first example of a product from a eukaryotic parasite that can directly interfere with antigen presentation, which, in turn, may suggest how filarial parasites might inactivate the host immune response to a helminth invader.
Asunto(s)
Presentación de Antígeno/inmunología , Antígenos de Diferenciación de Linfocitos B/inmunología , Brugia Malayi/inmunología , Cistatinas/inmunología , Inhibidores de Cisteína Proteinasa/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Proteínas de Plantas , Animales , Presentación de Antígeno/efectos de los fármacos , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Antígenos de Diferenciación de Linfocitos B/farmacología , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Catepsina B/antagonistas & inhibidores , Catepsinas/antagonistas & inhibidores , Línea Celular Transformada , Cisteína Endopeptidasas/metabolismo , Inhibidores de Cisteína Proteinasa/farmacología , Epítopos de Linfocito T/inmunología , Antígenos de Histocompatibilidad Clase II/farmacología , Humanos , Papaína/antagonistas & inhibidores , Fragmentos de Péptidos/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Toxina Tetánica/inmunologíaRESUMEN
Many parasitic nematodes live for surprisingly long periods in the tissues of their hosts, implying sophisticated mechanisms for evading the host immune system. The nematode Toxocara canis survives for years in mammalian tissues, and when cultivated in vitro, secretes antigens such as TES-32. From the peptide sequence, we cloned TES-32 cDNA, which encodes a 219 amino-acid protein that has a domain characteristic of host calcium-dependent (C-type) lectins, a family of proteins associated with immune defence. Homology modelling predicted that TES-32 bears remarkable structural similarity to mammalian immune-system lectins. Native TES-32 acted as a functional lectin in affinity chromatography. Unusually, it bound both mannose- and galactose-type monosaccharides, a pattern precluded in mammalian lectins by a constraining loop adjacent to the carbohydrate-binding site. In TES-32, this loop appeared to be less obtrusive, permitting a broader range of ligand binding. The similarity of TES-32 to host immune cell receptors suggests a hitherto unsuspected strategy for parasite immune evasion.
Asunto(s)
Lectinas/genética , Toxocara canis/inmunología , Secuencia de Aminoácidos , Animales , Antígenos Helmínticos/química , Antígenos Helmínticos/clasificación , Antígenos Helmínticos/genética , Sitios de Unión , Clonación Molecular , ADN Complementario/genética , ADN de Helmintos/genética , Genes de Helminto , Proteínas del Helminto/genética , Proteínas del Helminto/inmunología , Proteínas del Helminto/metabolismo , Humanos , Lectinas/clasificación , Lectinas/metabolismo , Mamíferos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , Homología de Secuencia de Aminoácido , Toxocara canis/genética , Toxocara canis/patogenicidadRESUMEN
The profile of global health today presents a striking reciprocal distribution between parasitic diseases in many of the world's lower-income countries, and ever-increasing levels of inflammatory disorders such as allergy, autoimmunity and inflammatory bowel diseases in the more affluent societies. Attention is particularly focused on helminth worm parasites, which are associated with protection from allergy and inflammation in both epidemiologic and laboratory settings. One mechanistic explanation of this is that helminths drive the regulatory arm of the immune system, abrogating the ability of the host to expel the parasites, while also dampening reactivity to many bystander specificities. Interest has therefore heightened into whether helminth parasites, or their products, hold therapeutic potential for immunologic disorders of the developed world. In this narrative review, progress across a range of trials is discussed, together with prospects for isolating individual molecular mediators from helminths that may offer defined new therapies for inflammatory conditions.
Asunto(s)
Enfermedades Autoinmunes/prevención & control , Helmintiasis/inmunología , Hipersensibilidad/prevención & control , Tolerancia Inmunológica , Ensayos Clínicos como Asunto , HumanosRESUMEN
Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency.
Asunto(s)
Inmunidad Mucosa/efectos de los fármacos , Macrófagos/inmunología , Nematospiroides dubius/inmunología , Infecciones por Strongylida/inmunología , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Neutralizantes/farmacología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , Granulocitos/parasitología , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-2/farmacología , Subunidad alfa del Receptor de Interleucina-2/antagonistas & inhibidores , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Nematospiroides dubius/efectos de los fármacos , Carga de Parásitos , Transducción de Señal , Infecciones por Strongylida/tratamiento farmacológico , Infecciones por Strongylida/parasitología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/parasitología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/parasitología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th17/parasitología , Factores de Transcripción/genética , Factores de Transcripción/inmunologíaRESUMEN
Human lymphatic filariasis is a chronic, potentially debilitating disease caused by Brugia and Wuchereria species of parasitic nematodes. The spectrum of clinical manifestations appears to be related to the immune response of individuals to invasive larvae, adult worms and circulating first-stage larvae (microfilariae). Potential immunopathological outcomes place constraints on vaccine development, emphasizing the need to understand the basis of immunity and pathology. Clones coding for a number of distinct antigenic proteins of Brugia pahangi and Brugia malayi have been isolated via immunological screening of a cDNA expression library. A small number of these expressed peptides show exclusive reactivity with antibody from amicrofilaraemic, potentially immune individuals. Surprisingly, a dominant immunogen isolated with human antibody is the filarial parasite homologue of heat shock protein (hsp) 70. This protein is constitutively expressed in both insect- and mammalian-dwelling parasitic stages, but does not appear to presented to the host immune system in intact worms.
Asunto(s)
Brugia/genética , Secuencia de Aminoácidos , Animales , Antígenos Helmínticos/genética , Brugia/inmunología , Filariasis Linfática/inmunología , Proteínas de Choque Térmico/genética , Humanos , Datos de Secuencia MolecularRESUMEN
Toxocara canis larvae, infective to Man, secrete a number of antigenic macromolecules into culture medium over prolonged periods of time. These antigens have been collected and characterised with respect to molecular weight by sodium dodecyl sulphate-polyacrylamide gel electrophoresis following extrinsic and intrinsic radiolabelling, or electrophoresis followed by gel staining or immunoblotting. Panels of enzymes and lectins have been applied to examine protease sensitivity and carbohydrate composition, respectively, and a number of other biochemical data have been noted. Taken together, the excretory-secretory molecules contain more than 40% carbohydrate of which the majority is N-acetylgalactosamine and galactose. The individual antigens may readily be separated by gel filtration on a Sepharose 6B column, and it is shown that the major excretory-secretory macromolecules are all glycoproteins which differ in essential characteristics. For example, the 32 kDa antigen (TES-32) binds concanavalin A, is sensitive to a range of proteases and is the band most readily stained by silver and Coomassie blue. Both TES-120 and TES-400 components are resistant to tryptic or peptic cleavage, bind to Helix pomatia lectin and stain with periodic acid-Schiff, yet unlike TES-120, TES-400 does not incorporate radioactive methionine nor can it be stained by silver stain techniques. Finally, one protease, staphylococcal V8, reveals cleavage sites only in the TES-70 and TES-400 molecules.
Asunto(s)
Antígenos Helmínticos/análisis , Glicoproteínas/análisis , Proteínas del Helminto , Toxocara/inmunología , Acetilgalactosamina/análisis , Animales , Antígenos Helmínticos/metabolismo , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Femenino , Galactosa/análisis , Técnicas de Inmunoadsorción , Larva , Péptido Hidrolasas/metabolismo , Toxocara/análisisRESUMEN
The surface antigens of adult worms of the filarial nematode Brugia pahangi have been investigated further by surface radioiodination and detergent solubilisation techniques. In addition to yielding new information on the distribution of antigenic components of this stage, detergent-solubilised molecules were used in both radiometric and enzyme-linked assays for human and mouse antibody. These assays were subsequently used in screening for monoclonal antibodies from hybrid cells derived from animals infected with living parasites and boosted with detergent-extracted antigen. Three monoclonal antibody-producing cell lines were isolated, with differing antigenic specificities: Bp-1, which binds a non-iodinatable antigen with high ELISA activity; Bp-2, which reacts with a determinant found on but not unique to the major surface Iodogen-labelled 29 kDa antigen; and Bp-3, which is specific for a minor antigen of 20 kDa revealed by Iodogen labelling.