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1.
Vet Sci ; 11(2)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38393087

RESUMO

In our study, we explored how parasitic nematodes, specifically Heligmosomoides polygyrus, influence the immune response, focusing on their potential role in tumor growth. The study aimed to understand the mechanisms by which these parasites modify immune cell activation, particularly in macrophages, and how this might create an environment conducive to tumor growth. Our methods involved analyzing the effects of H. polygyrus excretory-secretory antigens on macrophage activation and their subsequent impact on breast cancer cell lines EMT6 and 4T1. We observed that these antigens significantly increased the expression of genes associated with both pro-inflammatory and anti-inflammatory molecules, such as inducible nitric oxide synthase, TNF-α, (Tumor Necrosis Factor) Il-6 (Interleukin), and arginase. Additionally, we observed changes in the expression of macrophage surface receptors like CD11b, F4/80, and TLR4 (Toll-like receptor 4). Our findings indicate that the antigens from H. polygyrus markedly alter macrophage behavior and increase the proliferation of breast cancer cells in a laboratory setting. This study contributes to a deeper understanding of the complex interactions between parasitic infections and cancer development, highlighting the need for further research in this area to develop potential new strategies for cancer treatment.

2.
Int J Mol Sci ; 24(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37762297

RESUMO

Parasitic helminths induce a transient, short-term inflammation at the beginning of infection, but in persistent infection may suppress the systemic immune response by enhancing the activity of regulatory M2 macrophages. The aim of the study was to determine how nematode infection affects age-related neuroinflammation, especially macrophages in the nervous tissue. Here, intraperitoneal LPS-induced systemic inflammation resulting in brain neurodegeneration was enhanced by prolonged Heligmosomoides polygyrus infection in C57BL/6 mice. The changes in the brain coincided with the increase in M1 macrophages, reduced survivin level, enhanced APP and GFAP expression, chitin-like chains deposition in the brain and deterioration behaviour manifestations. These changes were also observed in transgenic C57BL/6 mice predisposed to develop neurodegeneration typical for Alzheimer's disease in response to pathogenic stimuli. Interestingly, in mice infected with the nematode only, the greater M2 macrophage population resulted in better results in the forced swim test. Given the growing burden of neurodegenerative diseases, understanding such interactive associations can have significant implications for ageing health strategies and disease monitoring.


Assuntos
Envelhecimento , Lipopolissacarídeos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Lipopolissacarídeos/toxicidade , Inflamação
3.
J Adv Res ; 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37467960

RESUMO

INTRODUCTION: Intestinal parasitic infections are neglected diseases and, due to the increasing resistance of parasites to available drugs, they pose an increasing therapeutic challenge. Therefore, there is a great need for finding new compounds with antiparasitic activity. OBJECTIVES: In this work, new thiosemicarbazide and 1,2,4-triazole derivatives were synthesized and tested for their anthelmintic activity. METHODS: The synthesis was carried out by classical methods of organic chemistry. Anthelmintic activity tests were carried out in vitro (Rhabditis sp., Haemonchus contortus, Strongylidae sp.) in vitro (Heligmosomoides polygyrus/bakeri), and in silico analysis was performed. RESULTS: Quinoline-6-carboxylic acid derivative compounds were designed and synthesized. The highest activity in the screening tests in the Rhabditis model was demonstrated by compound II-1 with a methoxyphenyl substituent LC50 = 0.3 mg/mL. In the next stage of the research, compound II-1 was analyzed in the H. contortus model. The results showed that compound II-1 was active and had ovicidal (percentage of dead eggs > 45 %) and larvicidal (percentage of dead larvae > 75 %) properties. Studies in the Strongylidae sp. model confirmed the ovicidal activity of compound II-1 (percentage of dead eggs ≥ 55 %). In vivo studies conducted in the H. polygyrus/bakeri nematode model showed that the number of nematodes decreased by an average of 30 % under the influence of compound II-1. In silico studies have shown two possible modes of action of compound II-1, i.e. inhibition of tubulin polymerization and SDH. The test compound did not show any systemic toxic effects. Its influence on drug metabolism related to the activity of cytochrome CYP450 enzymes was also investigated. CONCLUSION: The results obtained in the in vitro, in vivo, and in silico studies indicate that the test compound can be described as a HIT, which in the future may be used in the treatment of parasitic diseases in humans and animals.

4.
Life (Basel) ; 13(2)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36836678

RESUMO

Accumulating data suggest an important role of growth factors in autoimmune diseases and parasitic nematode infections. Nematodes are used in clinical studies of autoimmune diseases and parasite-derived molecules are widely studied for their therapeutic potential in various types of disorders. However, the effect of nematode infection on growth factors in autoimmune disorders has not been studied. The objective of this study was to evaluate the influence of infection with the intestinal nematode Heligmosomoides polygyrus in murine autoimmune models on the production of growth factors. Here, the level of a variety of growth factors related mainly to angiogenesis was evaluated by protein array in the intestinal mucosa of C57BL/6 dextran sodium sulfate-induced colitic mice and in cerebral spinal fluid of experimental autoimmune encephalomyelitis (EAE) mice infected with nematodes. In addition, vessel formation was evaluated in the brains of EAE mice infected with H. polygyrus. A significant influence of nematode infection on the level of angiogenic factors was observed. Parasitic infection of colitic mice resulted in upregulation of mucosal AREG, EGF, FGF-2, and IGFBP-3 in the intestine of the host and better adaptation (infectivity). In EAE mice, infection increased the level of FGF-2 and FGF-7 in CSF. In addition, remodeling of brain vessels was observed, with a higher density of long vessels. Nematode-derived factors are promising tools to fight autoimmune diseases and to study angiogenesis.

5.
Oxid Med Cell Longev ; 2022: 1799839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478989

RESUMO

Muscle larva of the parasitic nematode Trichinella spp. lives in a portion of muscle fibre transformed to a nurse cell (NC). Based on our previous transcriptomic studies, NC growth arrest was inferred to be accompanied by cellular senescence. In the current study, NC was proven to display the following markers of senescence: high senescence-associated ß-galactosidase activity, lipid deposition, DNA damage, and cell cycle inhibition. Moreover, the nuclear localization of Activator Protein 1 (c-Fos, c-Jun, and FosB), as well as the upregulation of numerous AP-1 target genes in the NC, remained in accord with AP-1 recently identified as a master transcription factor in senescence. An increase in reactive oxygen species generation and the upregulation of antioxidant defence enzymes, including glutathione peroxidases 1 and 3, catalase, superoxide dismutases 1 and 3, and heme oxygenase 1, indicated an ongoing oxidative stress to proceed in the NC. Interestingly, antioxidant defence enzymes localized not only to the NC but also to the larva. These results allowed us to hypothesize that oxidative stress accompanying muscle regeneration and larval antigenic properties lead to the transformation of a regenerating myofibre into a senescent cell. Cellular senescence apparently represents a state of metabolism that sustains the long-term existence of muscle larva and ultimately provides it with the antioxidant capacity needed during the next host colonization. Senotherapy, a therapeutic approach aimed at selective elimination of senescent cells, can thus be viewed as potentially effective in the treatment of trichinosis.


Assuntos
Trichinella , Animais , Larva , Fator de Transcrição AP-1 , Músculos , Senescência Celular , Mamíferos
6.
Pathogens ; 10(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806494

RESUMO

The influence of triterpenoid saponins on subcellular morphological changes in the cells of parasitic nematodes remains poorly understood. Our study examines the effect of oleanolic acid glucuronides from marigold (Calendula officinalis) on the possible modification of immunogenic proteins from infective Heligmosomoides polygyrus bakeri larvae (L3). Our findings indicate that the triterpenoid saponins alter the subcellular morphology of the larvae and prevent recognition of nematode-specific proteins by rabbit immune-IgG. TEM ultrastructure and HPLC analysis showed that microtubule and cytoskeleton fibres were fragmented by saponin treatment. MASCOT bioinformatic analysis revealed that in larvae exposed to saponins, the immune epitopes of their proteins altered. Several mitochondrial and cytoskeleton proteins involved in signalling and cellular processes were downregulated or degraded. As possible candidates, the following set of recognised proteins may play a key role in the immunogenicity of larvae: beta-tubulin isotype, alpha-tubulin, myosin, paramyosin isoform-1, actin, disorganized muscle protein-1, ATP-synthase, beta subunit, carboxyl transferase domain protein, glutamate dehydrogenase, enolase (phosphopyruvate hydratase), fructose-bisphosphate aldolase 2, tropomyosin, arginine kinase or putative chaperone protein DnaK, and galactoside-binding lectin. Data are available via ProteomeXchange with identifier PXD024205.

7.
Dev Comp Immunol ; 115: 103879, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007336

RESUMO

The mouse intestinal parasite Heligmosomoides polygyrus demonstrates adaptation to the inflammatory milieu as a result of colitis induced by dextran sulphate sodium (DSS). Nematodes from mice with colitis had different effects on dendritic cells than nematodes from mice without colitis. Immature JAWSII cells pre-exposed to L4 stage H. polygyrus from DSS-treated mice were adoptively transferred to mice with induced colitis. After two days, a higher disease activity index, macroscopic damage score and colon histology score were observed. MLN T cells isolated nine days after transfer demonstrated proinflammatory IFN-γ and IL-17 production. Transfer of JAWSII stimulated with male or female L4 larvae from a control invasion resulted in a slight improvement of colitis; in addition, dendritic cells exposed to H. polygyrus female L4 larvae, provoked migration of CD8+CD25+ T cells from MLN to the colon. Nematodes from an inflammatory environment changed cytokine production by dendritic cells. Inflammatory milieu changing nematode immunomodulatory activity affects dendritic cell functions, which offers new insight into the helminth-host relationship.


Assuntos
Colite/terapia , Células Dendríticas/imunologia , Nematospiroides dubius/imunologia , Terapia com Helmintos/métodos , Transferência Adotiva , Animais , Movimento Celular/imunologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Parasita/imunologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Larva , Linfonodos/citologia , Linfonodos/imunologia , Masculino , Mesentério , Camundongos , Cultura Primária de Células , Fatores Sexuais , Linfócitos T/imunologia
8.
Parasitology ; 147(13): 1480-1487, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32729450

RESUMO

The gastrointestinal nematode Heligmosomoides polygyrus bakeri shows enhanced survival in mice with colitis. As the antibody response plays an important role in antiparasitic immunity, antibodies against male and female L4 H. polygyrus were examined in mice with and without colitis. Levels of specific antibodies in the mucosa and serum were determined by enzyme-linked immunosorbent assay and immunogenic proteins of male and female parasites were identified using 2D electrophoresis and mass spectrometry. The function of identified proteins was explored with Blast2Go. Nematodes in mice with colitis induced higher levels of specific immunoglobulin G (IgG1) and IgA, a lower level of IgE in the small intestine and a higher level of IgE in serum against female L4. Infected mice with colitis recognized 12 proteins in male L4 and 10 in female L4. Most of the recognized proteins from male L4 were intermediate filament proteins, whereas the proteins from female L4 were primarily actins and galectins. Nematodes from mice with colitis were immunogenically different from nematodes from control mice. This phenomenon gives new insights into helminth therapy as well as host-parasite interactions.


Assuntos
Anticorpos Anti-Helmínticos/imunologia , Colite/imunologia , Proteínas de Helminto/imunologia , Nematospiroides dubius/fisiologia , Proteoma/imunologia , Infecções por Strongylida/imunologia , Animais , Colite/parasitologia , Feminino , Intestinos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Strongylida/parasitologia
9.
Parasite Immunol ; 42(5): e12704, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32049381

RESUMO

Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of monocyte and granulocyte progenitors that are highly suppressive against T cells. In BALB/c mice infected with a nematode Heligmosomoides polygyrus bakeri, we studied the dynamics of MDSCs, identified as CD11b+Gr-1+, induction in different tissues along with the development of parasite infection. We observed that MDSC-like cells are induced both by larvae and adult stages of H polygyrus bakeri. Gr-1+ cells of suppressive phenotype are recruited in the bone marrow, peripheral blood and peritoneal cavity during histotropic phase of infection and are present at that time in the intestine wall, where worms reside. Later, during intestinal phase, suppressive Gr-1+ cells increased in mesenteric lymph nodes and the spleen. l-arginine metabolism was important for the protective immunity, and parasite-induced Gr-1+ cells showed elevated arginase-1 and iNOS expression. Inhibition of arginase-1 and l-arginine administration caused reduced level of infection that coincided with weaker suppressive phenotype of Gr-1+ cells. We identified that l-arginine pathway activation and induction of MDSC-like cells characterize immunosuppressive state during H polygyrus bakeri infection in mice. Our findings confirm the role of MDSCs in parasitic infections and point l-arginine pathway as a potential target for immunomodulation during nematode infections.


Assuntos
Arginina/imunologia , Antígeno CD11b/imunologia , Monócitos/imunologia , Nematospiroides dubius/imunologia , Receptores de Quimiocinas/imunologia , Infecções por Strongylida/imunologia , Animais , Antígeno CD11b/genética , Feminino , Humanos , Tolerância Imunológica , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/parasitologia , Nematospiroides dubius/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Receptores de Quimiocinas/genética , Baço/imunologia , Infecções por Strongylida/genética , Infecções por Strongylida/parasitologia
10.
Immunobiology ; 224(6): 817-826, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31466733

RESUMO

The experimental autoimmune encephalomyelitis (EAE) animal model of Multiple Sclerosis (MS) is characterized by episodic neurologic dysfunction arising as a consequence of perivascular mononuclear cell infiltration and demyelination in the CNS. Leukocyte integrins, which are responsible for migration through the endothelial, play key roles in the pathogenesis of autoimmune diseases and chronic inflammation. Intestinal infection of mice with Heligmosomoides polygyrus appears to target CD11b (integrin αM), which is highly expressed on myeloid cells and is critical for their migration and function. H. polygyrus infection induces suppression of ongoing experimental EAE and extensive infiltration of CD11b+ cells to the CNS. Therefore, the aim of the present study was to characterize the phenotype and activity of CD11b+ cells accompanying the tissue phase infection of L4 H. polygyrus in EAE mice. It was found that the cells displayed a CD11b+ state with a distinct phenotype characterised by the expression of co-stimulatory CD80/CD86, CD40, MHCII, F4/80 and the mannose receptor CD206. This activation state illustrates the heterogeneity of CD11b+ cells in EAE mice following nematode invasion; these may have important consequences for understanding the effects of CD11b integrin, which is involved in the downregulation of neuroinflammatory disorders.


Assuntos
Antígeno CD11b/imunologia , Encefalomielite Autoimune Experimental/imunologia , Nematospiroides dubius , Animais , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Feminino , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito
11.
Exp Parasitol ; 196: 12-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30465732

RESUMO

Helminths and their products are strong candidates for the treatment of autoimmunological disorders and allergies. Being a key population of antigen-presenting cells, dendritic cells play a crucial role in the therapeutic potential of worms. The study compares the effects of live pre-male and pre-female L4 stage Heligmosomoides polygyrus administration on the maturation and activation of the JAWS II line of immature dendritic cells. On stimulation with L4 stage H. polygyrus, JAWS II cells acquire semi-mature status and induce Th2 and regulatory responses in vitro. The strongest immunosuppressive effect on JAWS II cells was observed following stimulation with both sexes of nematodes together; this was manifested as immature dendritic cell morphology, proliferation inhibition, cell cycle change, decreased translocation of NF-κB into the nucleus, and lower expression of surface cellular costimulatory molecules CD80, CD86 and MHC I. However, greater production of proinflammatory (IL-12p70, TNF-α, IL-6) and Th2 response-promoting cytokines (IL-4) was observed by JAWS II following exposure to both sexes compared to male or female larvae alone. Sex had no influence on the viability, apoptosis process or endocytosis abilities of the JAWS II cell line. The findings indicate that the presence of only a single sex of the parasite influences a developed response, resulting in reduced proinflammatory and an antiparasitic reaction.


Assuntos
Células Dendríticas/parasitologia , Nematospiroides dubius/fisiologia , Animais , Apoptose , Células da Medula Óssea/imunologia , Células da Medula Óssea/parasitologia , Células da Medula Óssea/fisiologia , Ciclo Celular , Linhagem Celular , Quimiocinas/análise , Citocinas/análise , Células Dendríticas/imunologia , Células Dendríticas/fisiologia , Endocitose , Feminino , Larva/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/análise , Nematospiroides dubius/crescimento & desenvolvimento , Fatores Sexuais , Organismos Livres de Patógenos Específicos
12.
Arch Immunol Ther Exp (Warsz) ; 66(3): 231-243, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28975357

RESUMO

Helminths use various immunomodulatory and anti-inflammatory strategies to evade immune attack by the host. During pathological conditions, these strategies alter the course of disease by reducing immune-mediated pathology. The study examines the therapeutic effect of the nematode L4 stage based on an in vivo model of multiple sclerosis, monophasic encephalomyelitis (EAE), induced by sensitization with MOG35-55 peptide in C57BL/6 female mice infected with the intestinal nematode Heligmosomoides polygyrus. The EAE remission was correlated with altered leukocyte number identified in the central nervous system (CNS), and temporary permeability of the blood-brain barrier at the histotrophic phase of infection. At 6 days post-infection, when the L4 stage had almost completely attenuated the clinical severity and pathological signs of EAE, CD25+ cell numbers expanded significantly, with parallel growth of CD8+ and CD4+, both CD25+Foxp3+ and CD25+Foxp3- subsets and alternatively activated macrophages. The phenotypic changes in distinct subsets of cerebrospinal fluid cells were correlated with an inhibited proliferative response of encephalitogenic T cells and elevated levels of nerve growth factor and TGF-ß. These results enhance our understanding of mechanisms involved in the inhibition of immune responses in the CNS during nematode infection.


Assuntos
Sistema Nervoso Central/imunologia , Encefalomielite Autoimune Experimental/imunologia , Intestinos/imunologia , Esclerose Múltipla/imunologia , Nematospiroides dubius/fisiologia , Infecções por Strongylida/imunologia , Linfócitos T Reguladores/imunologia , Animais , Barreira Hematoencefálica , Sistema Nervoso Central/parasitologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/parasitologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunomodulação , Intestinos/parasitologia , Estágios do Ciclo de Vida , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/parasitologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Fator de Crescimento Neural/metabolismo , Fragmentos de Peptídeos/imunologia , Fator de Crescimento Transformador beta/metabolismo
13.
Ann Parasitol ; 63(3): 223­227, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29274217

RESUMO

Babesiosis is an emerging, tick-transmitted disease caused by the intraerythrocytic parasite Babesia microti. In immunocompetent individuals, B. microti infection quickly resolves after antibabesial treatment. Immunocompromised patients and those of advanced age experience chronic and relapsing babesiosis, accompanied by severe complications and often, a fatal outcome. In these individuals, B. microti infection may persist despite multiple courses of treatment with antiprotozoal drugs. The increasing incidence of human babesiosis caused by B. microti, coupled with a growing number of immunosuppressed people who do not respond to standard antibabesial therapy, emphasises the need for new therapeutics for this protozoan infection with more effective mechanisms of action. Plasmodione, namely 3-[4-(trifluoromethyl)benzyl]-menadione, acts as a redox cycler and disrupts the redox homeostasis of Plasmodium-infected erythrocytes. The present study was designed to evaluate the potential inhibitory effect of this novel antimalarial compound against intraerythrocytic stages of B. microti in mice. Our results demonstrate that plasmodione did not reduce the level of parasitemia in B. microti-infected mice, indicating that interfering with the parasite redox balance is not an effective strategy to restrict the division of this protozoan. The mechanism of parasite resistance to plasmodione may be based on the differences in the oxidative metabolisms of Babesia and Plasmodium parasites inside infected erythrocytes. The significance of our results is discussed in relation to the development of novel antibabesial drugs based on redox-active benzylmenadiones.


Assuntos
Antimaláricos/uso terapêutico , Babesia microti , Babesiose/tratamento farmacológico , Vitamina K 3/análogos & derivados , Animais , Antimaláricos/farmacologia , Babesiose/parasitologia , Camundongos , Oxirredução , Vitamina K 3/uso terapêutico
14.
Molecules ; 22(11)2017 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-29156562

RESUMO

The purpose of this study was to evaluate the potential of chitosan units released during natural degradation of the polymer to activate the immune system against T. spiralis infection. High molecular weight chitosan was injected intraperitoneally into C57BL/6 mice. Flow cytometry and cytokine concentration, measured by ELISA, were used to characterize peritoneal cell populations during T. spiralis infection. The strong chemo-attractive properties of chitosan caused considerable infiltration into the peritoneal cavity of CD11b⁺ cells, with reduced expression of MHC class II, CD80, CD86, Dectin-1 or CD23 receptors in comparison to T. spiralis-infected mice. After prolonged chitosan biodegradation, cell populations expressing IL-4R, MR and Dectin-1 receptors were found to coexist with elevated IL-6, IL-10, TGF-ß and IgA production. IgA cross-reacted with T. spiralis antigen and chitosan. It was found that chitosan treatment attracted immune cells with low activity, which resulted in the number of nematodes increasing. The glucosamine and N-acetyl-D-glucosamine residues were recognized by wheat germ agglutinin (WGA) lectin and therefore any biodegradable chitosan units may actively downregulate the immune response to the parasite. The findings are relevant for both people and animals treated with chitosan preparations.


Assuntos
Quitosana/metabolismo , Quitosana/uso terapêutico , Trichinella spiralis/efeitos dos fármacos , Trichinella spiralis/imunologia , Animais , Imunoglobulina A/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Fator de Crescimento Transformador beta/metabolismo
15.
Vet Parasitol ; 241: 5-13, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28579031

RESUMO

Avena sativa L., 1753 (Poaceae) is used as feed for livestock and as a crop rotation agent. The purpose of the study was to examine the molecular mechanisms behind the antihelminth activity of the oat saponins avenacoside B (AveB) and 26-desglucoavenacoside B (26DGAveB) by evaluating their effect on Heligmosomoides bakeri, a parasitic nematode of mice. The avenacosides AveB and 26DGAveB were separated and purified from A. sativa green leaves, and their mycotoxic activity was confirmed against the fungus Trichoderma harzianum. The anti-nematode activity of the avenacosides was measured by egg hatching assay. In the surviving L3 larvae exposed to avenacosides, the expression of CED-9, a protein of the apoptosis pathway, was identified by Western blotting. The protein profile of L3 larvae was monitored by High Performance Liquid Chromatography (HPLC). The action of saponins on glycoprotein pump (Pgp) activity in L3 larvae was compared to that of the pump blocker Verapamil (VPL). A mouse model was used to measure the infectivity of L3 larvae exposed to AveB and 26DGAveB, and the outcome of the immune response. Both compounds induced morphological changes in larvae and blocked Pgp activity; however, only 26DGAveB provoked expression of CED-9. The infected mice displayed changes in the molecular pattern of larval proteins and enhanced IL-4 production, indicating that avenacosides reduced the infectivity of H. bakeri larvae. In avenacosides, the residue without glucose at the C26 position demonstrated greater anti-nematode activity. Our findings indicate that A. sativa compounds are natural products with anti-parasitic activity.


Assuntos
Anti-Helmínticos/farmacologia , Heligmosomatoidea/efeitos dos fármacos , Saponinas/farmacologia , Infecções por Strongylida/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Anti-Helmínticos/química , Avena/química , Caenorhabditis elegans/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Larva/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Saponinas/química
16.
Ann Parasitol ; 63(1): 7-14, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28432858

RESUMO

It is estimated that more than half of the nowadays known species are pathogenic parasites. Among macroparasites gastrointestinal nematodes are one of most common and having significant impact on life and health. Those organisms reveal strong, specific immune response in host, involving primary mechanisms associated with regulatory and Th2 cells. Referring to immunomodulatory abilities of helminths, parasite infections started to be considered as a possible therapy for many autoimmune diseases. Clinical trials on 2nd and 3rd stage are conducted in spite that treatment has not been recognized as safe for common use. Despite that the safety of treatment with parasites is still controversial and widely discussed. Our knowledge about mechanisms used by helminth to moderate immune response is still inadequate to predict possible effect of long lasting parasite infection on individual patients.


Assuntos
Doenças Autoimunes/patologia , Doenças Parasitárias/complicações , Animais , Doenças Autoimunes/parasitologia , Humanos
17.
Acta Parasitol ; 60(2): 337-44, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26204004

RESUMO

The probability of infection with fungi, as well as parasitic nematodes or arthropods may increase in overcrowded population of animals and human. The widespread overuse of drugs and immunosuppressants for veterinary or medical treatment create an opportunity for many pathogenic species. The aim of the review is to present the common molecular characteristics of such pathogens as fungi and nematodes and other chitin bearing animals, which may both activate and downregulate the immune response of the host. Although these pathogens are evolutionary distinct and distant, they may provoke similar immune mechanisms. The role of chitin in these phenomena will be reviewed, highlighting the immune reactions that may be induced in mammals by this natural polymer.


Assuntos
Quitina/genética , Quitina/imunologia , Fungos/genética , Fungos/imunologia , Parasitos/genética , Parasitos/imunologia , Animais , Humanos , Tolerância Imunológica , Fatores Imunológicos/genética , Fatores Imunológicos/imunologia
18.
PLoS One ; 8(10): e78034, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167594

RESUMO

The precise mechanism of the very effective therapeutic effect of gastrointestinal nematodes on some autoimmune diseases is not clearly understood and is currently being intensively investigated. Treatment with living helminths has been initiated to reverse intestinal immune-mediated diseases in humans. However, little attention has been paid to the phenotype of nematodes in the IBD-affected gut and the consequences of nematode adaptation. In the present study, exposure of Heligmosomoides polygyrus larvae to the changed cytokine milieu of the intestine during colitis reduced inflammation in an experimental model of dextran sulphate sodium (DSS)- induced colitis, but increased nematode establishment in the moderate-responder BALB/c mouse strain. We used mass spectrometry in combination with two-dimensional Western blotting to determine changes in protein expression and changes in nematode antigens recognized by IgG1 in mice with colitis. We show that nematode larvae immunogenicity is changed by colitis as soon as 6 days post-infection; IgG1 did not recognize highly conserved proteins Lev-11 (isoform 1 of tropomyosin α1 chain), actin-4 isoform or FTT-2 isoform a (14-3-3 family) protein. These results indicate that changes in the small intestine provoked by colitis directly influence the nematode proteome. The unrecognized proteins seem to be key antigenic epitopes able to induce protective immune responses. The proteome changes were associated with weak immune recognition and increased larval adaptation and worm growth, altered localization in the intestine and increased survival of males but reduced worm fecundity. In this report, the mechanisms influencing nematode survival and the consequences of changed immunogenicity that reflect the immune response at the site colonized by the parasite in mice with colitis are described. The results are relevant to the use of live parasites to ameliorate IBD.


Assuntos
Adaptação Fisiológica/imunologia , Colite/imunologia , Interações Hospedeiro-Parasita/imunologia , Nematospiroides dubius/fisiologia , Infecções por Strongylida/imunologia , Proteínas 14-3-3/imunologia , Actinas/imunologia , Animais , Antígenos de Helmintos/imunologia , Colite/induzido quimicamente , Colite/parasitologia , Citocinas/imunologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Proteínas de Helminto/imunologia , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteoma/imunologia , Infecções por Strongylida/parasitologia , Tropomiosina/imunologia
19.
Exp Parasitol ; 135(3): 524-31, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24036322

RESUMO

Saponins of marigold (Calendula officinalis), in particular derivatives of 3-O-monoglucuronide of oleanolic acid, are able to reduce infectivity of Heligmosomoides polygyrus in mice. The purpose of this study was to understand the immune activation provoked by third-stage larvae exposed to marigold glucuronides. We also examined the pattern of glycosylation of larval antigens which appeared to be crucial for induction of cytokine production in BALB/c mice; higher concentrations of IL-6, IFN-γ, IL-10 and TNF-α were observed in serum or intestine one week post infection. Three weeks later, in the chronic phase of infection, cells in culture were able to produce IL-6, IFN-γ, TNF-α and IL-17. Restimulation of cells with H. polygyrus antigen resulted in reduced production of IL-6, and TNF-α. The pattern of cytokine production co-existed with reduced expression of terminal glucose, α-linked mannose, N-acetyl-galactosamine, ß-galactose, N-acetyl-glucosamine and α-fucose in several protein bands. Galactose, as a new terminal carbohydrate residue appeared in 20-24kDa protein bands. The number of immunogenic epitopes in parasitic antigens was reduced; only three protein bands of 56, 26 and 12kDa were recognized by IgG1. These studies provide a model system to find the glycosylated molecules expressed on nematodes that improve establishment and survival and characterize cytokine production in mice infected with larvae exposed to saponin. Identification of these molecules is the first step in the recognition of key antigenic epitopes able to induce protective or tolerogenic immune responses.


Assuntos
Glicoproteínas/química , Nematospiroides dubius/imunologia , Saponinas/farmacologia , Infecções por Strongylida/imunologia , Animais , Antígenos de Helmintos/análise , Antígenos de Helmintos/imunologia , Citocinas/metabolismo , Glucuronídeos/farmacologia , Glicoproteínas/efeitos dos fármacos , Glicoproteínas/imunologia , Glicosilação/efeitos dos fármacos , Soros Imunes/imunologia , Imunoglobulina G/imunologia , Larva/efeitos dos fármacos , Larva/imunologia , Larva/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nematospiroides dubius/efeitos dos fármacos , Nematospiroides dubius/metabolismo , Ácido Oleanólico/metabolismo , Ácido Oleanólico/farmacologia , Extratos Vegetais/farmacologia , Infecções por Strongylida/parasitologia , Tagetes/química
20.
Prion ; 7(4): 319-27, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23787700

RESUMO

Many laboratory studies and epidemiological observations confirm that nematodes prevent some immune-mediated diseases. The development of immunologically well-defined laboratory models of intestinal nematode infection has allowed significant advances to be made in understanding the immunological basis of effector mechanisms operating during infection under controlled laboratory conditions. The Heligmosomoides polygyrus- mouse system is used for studies of parasite immunomodulation. H. polygyrus causes a chronic, asymptomatic intestinal infection and effectively maintains both local and systemic tolerance to reduce allergic and autoimmune inflammation. However, exposure of mice to H. polygyrus antigen reduced spontaneous and glucocorticoid-induced apoptosis of CD4- positive T cells in mesenteric lymph node (MLN). In this study we evaluate the proliferation, cytokine secretion, cell cycle progression and expression of apoptosis related genes in MLN CD4 T cells of uninfected and H. polygyrus infected mice ex vivo and in vitro after restimulation with parasite excretory secretory antigen (ESAg), somatic antigen (SAg) and fraction 9 (F9Ag) of somatic antigen. For the first time we explain the influence of H. polygyrus antigens on the intrinsic pathway of apoptosis. We found that the proliferation provoked by fraction 9 and inhibition of apoptosis was dependent on a low Bax/Bcl-2 ratio, dramatical upregulation of survivin, D1 cyclin, P-glycoprotein, and loss of p27Kip1 protein with inhibition of active caspase-3 but not caspase- 8.


Assuntos
Antígenos de Helmintos/imunologia , Apoptose/imunologia , Linfócitos T CD4-Positivos/imunologia , Nematospiroides dubius/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Infecções por Strongylida/imunologia , Regulação para Cima/imunologia , Animais , Antígenos de Helmintos/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Infecções por Strongylida/metabolismo , Infecções por Strongylida/patologia
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