RESUMO
BACKGROUND: The neglected disease cystic echinococcosis is caused by larval Echinococcus granulosus flatworms, which form bladder-like hydatid cysts in liver, lungs, and other organs. SOURCES OF DATA: Published literature. AREAS OF AGREEMENT: Establishing larvae are susceptible to antibody-dependent killing, as attested by successful animal vaccination, whereas once established they are partially protected by the so-called laminated layer. Host responses are Th2 dominated, with a Th1 component. Diagnostic antigens from cyst fluid are known, but responses appear absent in one-fifth of patients. AREAS OF CONTROVERSY: Is evasion mainly based on induction of Th2 or regulatory responses by the parasite? GROWING POINTS: The parasite induces regulatory responses. The laminated layer has immune-regulatory properties. AREAS TIMELY FOR DEVELOPING RESEARCH: Develop tools for functional genomics; characterize immunologically interesting proteins suggested by genomic information; analyse infection in broader context of granulomatous responses; identify molecules secreted/excreted by intact larvae/cysts towards their outside, including diffusible immune-regulators.
Assuntos
Antígenos de Helmintos/imunologia , Equinococose/imunologia , Equinococose/parasitologia , Echinococcus granulosus/imunologia , Interações Hospedeiro-Parasita/imunologia , Animais , Antígenos de Helmintos/fisiologia , Proteínas de Helminto/fisiologia , Humanos , Imunidade Celular , LarvaRESUMO
Epidemiologic evidence has accumulated suggesting that helminth infection or their products protect against the development of autoimmune and allergic diseases. The mechanisms underlying this protection may include regulatory cells and cytokines. Both helminth infection and allergic diseases drive the immune system toward the Th2 type response with high production of IgE. However, while this antibody response is associated with the pathogenesis of allergic diseases, IgE production in regions endemic for parasite diseases, such as schistosomiasis, might be associated with a protection against infection. In individuals chronically exposed to Schistosoma sp infection, regulatory cells and cytokines which may develop to protect the host against harmful parasite antigens may also protect the host against allergic diseases. We have demonstrated that helminthic infections are associated with a poor response to allergy skin-prick tests and with low asthma pathology. This review summarizes the immune response that is associated with the pathology of allergic diseases such as asthma and with the resistance to helminth infections. Moreover, it is discussed how helminth infection, particularly Schistosoma mansoni or their products may influence the development of atopic asthma.
Assuntos
Antígenos de Helmintos/fisiologia , Asma/complicações , Hipersensibilidade/etiologia , Imunomodulação/fisiologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Animais , Antígenos de Helmintos/imunologia , Asma/imunologia , Humanos , Hipersensibilidade/imunologia , Modelos Biológicos , Schistosoma mansoni/fisiologiaRESUMO
Nematode infections induce the upregulation of mucin- and glycosylation-related genes in intestinal epithelial cells in vivo. However, the factor(s) that induce these changes in epithelial cells have not been fully elucidated. In the present study, we analysed the effects of the Th2 cytokines IL-4 and IL-13 and the excretory-secretory (ES) product of the nematode Nippostrongylus brasiliensis on the gene expression of the major mucin core peptide MUC2, the sialyltransferase ST3GalIV (Siat4c) and the sulphotransferase HS3ST1 in intestinal epithelium-derived IEC-6 cells by quantitative reverse transcription (RT)-PCR. The administration of IL-4 and IL-13 resulted in a significant upregulation of ST3GalIV and HS3ST1 gene transcription, but had no effect on MUC2, in IEC-6 cells. RT-PCR studies also demonstrated the constitutive expression of IL-13Ralpha1 and IL-4R in IEC-6 cells. On the other hand, the ES product induced upregulation of ST3GalIV, but not HS3ST1 or MUC2, while coadministration of IL-13 and the ES product induced a slight but significant upregulation of MUC2. Co-incubation of live N. brasiliensis adult worms with IEC-6 cells resulted in the upregulation of ST3GalIV and MUC2. These results suggested that HS3ST1 gene expression is strictly regulated by IL-4/IL-13, while ST3GalIV and MUC2 gene expressions are regulated by redundant mechanisms.
Assuntos
Íleo/parasitologia , Interleucina-13/fisiologia , Interleucina-4/fisiologia , Mucina-2/biossíntese , Nippostrongylus/patogenicidade , Sialiltransferases/biossíntese , Sulfotransferases/biossíntese , Animais , Antígenos de Helmintos/fisiologia , Células Epiteliais/imunologia , Células Epiteliais/parasitologia , Perfilação da Expressão Gênica , Íleo/imunologia , Masculino , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , beta-Galactosídeo alfa-2,3-SialiltransferaseRESUMO
To better understand the link between parasite infections and the course of multiple sclerosis (MS), we studied the role of TLRs in helminth product recognition by dendritic cells (DCs) and B cells. Baseline expression of TLR2 was significantly higher in infected-MS patients compared with uninfected MS subjects or healthy controls. Moreover, cells exposed to TLR2 agonists or to soluble egg Ag (SEA) from Schistosoma mansoni resulted in significant TLR2 up-regulation. SEA suppressed the LPS-induced DCs production of IL-1beta, IL-6, IL-12, and TNF-alpha and enhanced TGF-beta as well as IL-10 production. Similarly, after exposure to SEA, anti-CD40-activated B cells increased IL-10 production. Both processes were MyD88 dependent. In addition, SEA down-regulated the expression of LPS-induced costimulatory molecules on DCs in a MyD88-independent manner. DCs stimulation by SEA and TLR2 agonists induced increasing phosphorylation of the MAPK ERK1/2. Neither stimulus showed an effect on p38 and JNK1/2 phosphorylation, however. Addition of the ERK1/2 inhibitor U0126 was associated with dose-dependent inhibition of IL-10 and reciprocal enhancement of IL-12. Finally, cytokine effects and changes observed in DCs costimulatory molecule expression after SEA exposure were lost when TLR2 expression was silenced. Overall, these findings indicate that helminth molecules exert potent regulatory effects on both DCs and B cells through TLR2 regulation conducted via different signaling pathways. This knowledge could prove critical in developing novel therapeutic approaches for the treatment of autoimmune diseases such as MS.
Assuntos
Antígenos de Helmintos/fisiologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Receptor 2 Toll-Like/fisiologia , Adulto , Animais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Subpopulações de Linfócitos B/parasitologia , Células Cultivadas , Cisteína/análogos & derivados , Cisteína/farmacologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/parasitologia , Feminino , Humanos , Ligantes , Lipoproteínas/farmacologia , Masculino , Esclerose Múltipla/parasitologia , Óvulo/imunologia , Esquistossomose mansoni/metabolismo , Esquistossomose mansoni/patologia , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/biossíntese , Receptor 2 Toll-Like/metabolismoRESUMO
Eosinophils (Eo) are known to be important effector cells in the host defense against helminth parasites. Excretory-secretory products (ESP) released by helminths have shown wide immunomodulatory properties, such as the induction of cellular apoptosis. We investigated the ability of ESP from Fasciola hepatica to induce Eo apoptosis. In this work, we observed that ESP induced an early apoptosis of rat peritoneal eosinophils and that this phenomenon was time- and concentration-dependent. Furthermore, we demonstrated that activation of protein tyrosine kinases (TyrK) and caspases were necessary to mediate the Eo apoptosis induced by the ESP, and that carbohydrate components present in these antigens were involved in this effect. We have described for the first time the ability of ESP from F. hepatica to modify the viability of Eo by apoptosis induction. Besides that, we have observed Eo apoptosis in the liver of rats 21 days after F. hepatica infection. The diminution in Eo survival in early infection could be a parasite strategy in order to prevent a host immune response.
Assuntos
Antígenos de Helmintos/fisiologia , Apoptose , Caspases/metabolismo , Eosinófilos/imunologia , Eosinófilos/fisiologia , Fasciola hepatica/patogenicidade , Fasciolíase/imunologia , Animais , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Eosinófilos/parasitologia , Fasciola hepatica/imunologia , Fasciolíase/parasitologia , Fasciolíase/fisiopatologia , Microscopia Eletrônica de Transmissão , Proteínas Tirosina Quinases/metabolismo , RatosRESUMO
Among the most important aspects in the study of trichinosis are the development of specific and sensitive diagnostic methods for the detection of the infection by the parasite as well as the characterization of antigens from Trichinella spiralis that induce protection in the host. In the context, the characterization of surface stichosome and excretory secretory antigens of T. spiralis muscle larvae has been an important issue due to the high immunogenicity of such components in most hosts so far studied. In this work, we have been able to identify and characterize molecules from both compartments of muscle larvae. These components have been used in assays for specific detection of T. spiralis infections particularly in pigs, as well as in assays to evaluate their role in the induction of protection in mice.
Assuntos
Antígenos de Helmintos/análise , Trichinella spiralis/imunologia , Triquinelose/diagnóstico , Animais , Antígenos de Helmintos/fisiologia , Antígenos de Superfície , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Trichinella spiralis/crescimento & desenvolvimento , Triquinelose/imunologiaRESUMO
The reactivity of mononuclear cells (2 x 10**6/ml minimum Eagle's medium, MEM) from normal subjects and from Schistosoma mansoni-infected patients was evaluated by microcalorimetry. The results which are reported as heat production (mcal for 2 x 10**6 cells in 3600s), were 2,087 ñ 21.2 and 2,497.0 ñ 21.3 for mononuclear cells from infected patients (N = 8) under stimulation with S. mansoni soluble egg antigen (SEA) and soluble adult worm antigenic preparation (SWAP), respectively. The values for cells from normal subjects (N = 8) were 13.7 ñ 1.1 and 29.3 ñ 3.2 in the presence of the same antigens. Pre-treatment of mononuclear cells from patients with 1 mM aminophylline (a cAMP phospphodiesterase inhibitor) totally abolished heat production. Cell viability (> 95%) was not changed after the measurement. The microcalorimetric assay described here measures the cellular metabolic activity and we feed justified in suggesting this techinique as an auxiliary diagnosis of schistosomiasis. Given the sensitivity, precision and accuracy of this microcalorimetric assay, we feel it can be used for the diagnosis of disease conditions for which a reliable diagnostic method is required