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T cell proliferation assay. Cultivating CFSE-stained PBMCs in the presence of ES antigens revealed TcES to be capable of reducing PHA-induced lymphocyte proliferation (A) at 150 µg/mL and this was detectable in both CD4+ (B) and CD8+ (C) T cells. AcES showed similar effects in lymphocytes and CD4+ cells, while the anti-proliferative capability was lower with loss of statistical significance in CD8+ T cells. P-values were calculated according to one-way ANOVA followed by the Tukey's honest significant difference post-hoc test. Error bars represent standard error of mean (SEM). FSC = forward scatter, SSC = side scatter. Experiments were repeated six times at two different time points.
Source publication
Parasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present stu...
Context in source publication
Context 1
... carboxyfluorescein succinimidyl ester (CFSE)-labelled PBMCs were stimulated with phytohaemagglutinin-L (PHA-L) for 4 days and proliferation of lymphocytes as well as CD4 and CD8 subsets was then analysed using flow cytometry. This demonstrated pulsing with TcES at 150 µg/mL to significantly prevent mitogen-induced proliferation of lymphocytes ( Fig. 4A) and this effect was present in both CD4+ ( ELISA revealed both AcES and TcES to be capable of increasing IL-10 secretion by canine PBMCs. For AcES this effect was more obvious at 15 µg/mL. In contrast, TcES-associated IL-10 secretion was stronger at 150 µg/mL and was only detected when cells were co-stimulated with LPS. (B) For ...
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Citations
... In addition, some helminths can modulate the immune response by inducing the formation of T and B regulatory cells, which also produce IL-10 and TGF-β [27], the former being one of the strategies that help parasites evade the host immune response. In the case of T. canis infection in paratenic hosts, it has been determined that regulatory T cells participate in immunopathological events at the hepatic level from 5 weeks post-infection [28], while in definitive hosts it was shown that the secreted and excreted antigens of T. canis increase the frequency of regulatory T cells and the production of IL-10 [29]. ...
Background:
Toxocara canis (T. canis) is a helminth parasite of zoonotic and veterinary health significance that causes the disease known as Toxocariasis. This disease has been associated with conditions of poverty, especially in tropical climate zones throughout the world. Although it rarely causes important clinical manifestations, T. canis can lead to blindness, meningoencephalitis, or other nervous manifestations in humans. Moreover, some studies show its importance in the development of tumor growth, which have been associated with the parasite's ability to modulate the host's immune response. While different studies have evaluated the immune response during this disease, currently, there are no studies where the infection is analyzed from the perspective of sexual dimorphism.
Methods:
To evaluate sex differences in susceptibility, we analyzed lesions and parasite loads in lung and liver at 7 days post-infection. In addition, immune cell subpopulations were analyzed in spleen, mesenteric and peripheral lymph nodes. Finally, the production of cytokines and specific antibodies were determined in the serum. Statical analyses were performed using a Two-way ANOVA and a post-hoc Bonferroni multiple comparison test.
Results:
Female rats had a higher number of larvae in the liver, while male rats had them in the lungs. The percentages of immune cells were evaluated, and in most cases, no significant differences were observed. Regarding the cytokines production, infection can generate a decrease in Th1 such as IL-1β in both sexes and IL-6 only in females. In the case of Th2, IL-4 increases only in infected males and IL-5 increases in males while decreasing in females due to the effect of infection. IL-10 also decreases in both sexes as a consequence of the infection, and TGF-β only in females. Finally, the infection generates the production of antibodies against the parasite, however, their quantity is lower in females.
Conclusions:
This study demonstrates that T. canis infection is dimorphic and affects females more than males. This is due to a polarization of the inadequate immune response, which is reflected as a higher parasite load in this sex.
... When takins are compromised by other factors (such as parasites), bacteria exploit the opportunity to multiply and cause damage. Modulating and suppressing the immune system is a competitive advantage of many parasites, whereby they can influence the host's immune response (Junginger et al., 2017). At the same time, in the host, the parasite is affected by additional antimicrobial agents produced by the host immune system and competing gut microbiota (Palmer-Young et al., 2016). ...
Introduction
The intestinal tract of animals is a complex and dynamic microecosystem that is inextricably linked to the health of the host organism. Takin ( Budorcas taxicolor ) is a threatened species, and its gut microbiome is poorly understood. Therefore, this study aimed to analyze the microbial community structure and potential pathogens of takin.
Methods
Takin fecal samples were collected from five sites in a nature reserve to ensure the uniformity of sample collection, determine the effects of different geographical locations on gut microbes, and analyze the differences in microbial communities between sites. Subsequently, high-throughput 16S rDNA gene sequencing was performed to analyze the microbial diversity and potential pathogens in the gut; the findings were verified by isolating and culturing bacteria and metagenomic sequencing.
Results and discussion
The takin gut microflora consisted mainly of four phyla: Firmicutes (69.72%), Bacteroidota (13.55%), Proteobacteria (9.02%), and Verrucomicrobiota (3.77%), representing 96.07% of all microorganisms. The main genera were UCG-005 (20.25%), UCG-010_unclassified (12.35%), Firmicus_unclassified (4.03%), and Rumino coccsea_unclassified (3.49%), while the main species were assigned to Bacteria_unclassified . Potential pathogens were also detected, which could be used as a reference for the protection of takin. Pseudomonas presented the highest abundance at Shuichiping and may represent the main pathogen responsible for the death of takin at the site. This study provides an important reference for investigating the composition of the bacterial community in the intestine of takin.
... Worms and their derived proteins have been shown therapeutic effects on a variety of inflammatory or autoimmune diseases such as diabetes [23], multiple sclerosis [24], allergic rhinitis [25], systemic lupus erythematosus [26] and encephalomyelitis [27]. These effects are mainly achieved through immunomodulating host immune responses to inhibit inflammatory responses and promote regulatory immune responses including induction of M2 macrophages [28,29]. The helminth infection or derived products stimulate M2 macrophage polarization, which inhibits excessive inflammatory responses and promotes the healing and repair of the tissue damage caused by microbial infections [30,31] or metabolic diseases [32]. ...
Background
Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms ( Ts -AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts -AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment.
Methods
The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts -AES by intraperitoneal injection. The therapeutic effect of Ts -AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts -AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts -AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts -AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts -AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry.
Results
We observed that treatment with Ts -AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts -AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro.
Conclusions
Our results demonstrate that Ts -AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts -AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases.
Graphical Abstract
... Here, C. cellulosae ESAs induced Foxp3 expression in piglet lymphocytes, but the CAs showed no significant differences compared with those of the controls. These results are similar to those of a previous study on Toxocara canis ESAs in canine Foxp3 + Tregs (Junginger et al., 2017). The results showed that C. cellulosae ESAs may induce Treg production and exert immunosuppressive effects in natural hosts. ...
Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4⁺/CD8⁺ T-cell proportions, increased the CD4⁺Foxp3⁺ and CD8⁺Foxp3⁺ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4⁺ and CD4⁻CD8⁻ T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.
... In general, stimulation studies with antigens derived from helminths, including Toxocara spp., are challenging as these antigens seem to induce rather low levels of cytokine secretion and surface marker expression or even dampen effector functions of APCs [47]. This was also observed in other studies utilising canine monocyte-derived DCs or a human THP-1 macrophage cell line [23,48]. Thus, a co-stimulus, often LPS as a TLR4 agonist, inducing pro-inflammatory cytokine secretion is generally needed and was used for stimulation studies of WT and CLR −/− DCs. ...
... antigen stimulation. Junginger et al. [48] observed that T. canis TES prevented canine DCs from LPS-induced maturation as indicated by reduced MHC-II and CD86 surface marker expression. In the present study, TES stimulation had little to no effect on MHC-II surface marker expression of murine BMDCs. ...
Toxocara canis and Toxocara cati, the worldwide occurring intestinal roundworms of canids and felids, represent an important public health threat due to various disease manifestations in humans. Host recognition of pathogens is mediated by pattern recognition receptors (PRRs). Myeloid C-type lectin receptors (CLRs) are PRRs and recognise carbohydrate structures of various pathogens. As Toxocara excretory-secretory products (TES) are predominantly composed of glycoconjugates, they represent suitable targets for CLRs. However, the range of host-derived CLRs recognising Toxocara spp. is still unknown. Using a CLR-hFc fusion protein library, T. canis and T. cati L3 somatic antigens (TSOM) were bound by a variety of CLRs in enzyme-linked immunosorbent assay (ELISA), while their TES products interacted with macrophage galactose-type lectin-1 (MGL-1). Two prominent candidate CLRs, MGL-1 and macrophage C-type lectin (MCL), were selected for further binding studies. Immunofluorescence microscopy revealed binding of MGL-1 to the oral aperture of L3. Immunoblot experiments identified distinct protein fractions representing potential ligands for MGL-1 and MCL. To evaluate how these interactions influence the host immune response, bone marrow-derived dendritic cell (BMDC) assays were performed, showing MCL-dependent T. cati-mediated cytokine production. In conclusion, MGL-1 and MCL are promising candidates for immune modulation during Toxocara infection, deserving further investigation in the future.
... For instance, CD4 + Th2 responses were notably inhibited by myeloid-derived suppressor cells induced by primary Heligmosomoides polygyrus (HP) infection [15], and HP infection could also block T cell activation by promoting P-glycoprotein activity [16]. Moreover, recent studies demonstrated that ES products derived from GI nematodes contributed to suppressing host T cell responses, as exemplified by the inhibition of CD4 + and CD8 + T cell proliferation induced by Ancylostoma caninum and Toxocara canis ES proteins [17]. However, the exact role of T cells as putative key effector cells in H. contortus infection is still poorly understood, and the exact molecular basis of the regulation between T cells and HcESPs remains to be elucidated. ...
Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.
... Dendritic cells play an important role in the initiation and modification of helminth-specific immune responses, and are crucial to drive immunologic tolerance [14,28]. The maturational state of mammal DCs could be altered to two completely contrary directions by the mixed ESPs or single ESP content from different parasite species, either promoting maturation [29], or suppressing maturation [8,30]. FhESPs have been reported capable of impairing the ability of murine DCs being activated by TLR ligands and also their capacity to stimulate an allospecific response [9]. ...
Background:
Fasciola gigantica infection threatens the health of both humans and animals in the world. The excretory/secretory products (ESPs) of this fluke has been reported to impair the activation and maturation of immune cells. We have previously shown the influence of F. gigantica ESPs (FgESPs) on the maturation of buffalo dendritic cells (DCs). However, the underlying mechanisms remain unclear. The objective of this study was to investigate the potency of FgESPs in shifting the differentiation and immune functions of buffalo DCs.
Methods:
Buffalo DCs were incubated with FgESPs directly or further co-cultured with lymphocytes in vitro. qRT-PCR was employed to determine the gene expression profile of DCs or the mixed cells, and an ELISA was used to measure cytokine levels in the supernatants. Hoechst and Giemsa staining assays, transmission electron microscopy, caspase-3/7 activity test and histone methylation test were performed to determine DC phenotyping, apoptosis and methylation. To investigate the mechanism involved with DNA methylation, a Co-IP assay and immunofluorescent staining assay were performed to observe if there was any direct interaction between FgESPs and DNMT1/TET1 in buffalo DCs, while RNAi technology was employed to knockdown DNMT1 and TET1 in order to evaluate any different influence of FgESPs on DCs when these genes were absent.
Results:
qRT-PCR and ELISA data together demonstrated the upregulation of DC2 and Th2/Treg markers in DCs alone and DCs with a mixed lymphocyte reaction (MLR), suggesting a bias of DC2 that potentially directed Th2 differentiation in vitro. DC apoptosis was also found and evidenced morphologically and biochemically, which might be a source of tolerogenic DCs that led to Treg differentiation. In addition, FgESPs induced methylation level changes of histones H3K4 and H3K9, which correlate with DNA methylation. Co-IP and immunofluorescent subcellular localization assays showed no direct interaction between the FgESPs and DNMT1/TET1 in buffalo DCs. The productions of IL-6 and IL-12 were found separately altered by the knockdown of DNMT1 and TET1 in DCs after FgESPs treatment.
Conclusions:
FgESPs may induce the DC2 phenotype or the apoptosis of buffalo DCs to induce the downstream Th2/Treg response of T cells, possibly through a DNMT1- or TET1-dependent manner(s).
... Se conoce poco sobre la interacción de T. canis con el sistema inmune de los caninos. La mayoría de los estudios de este tipo se han documentado en ratones y en humanos (Junginger et al. 2017). Se reporta que los anticuerpos anti-Toxocara spp. ...
La toxocariasis es una enfermedad zoonótica cosmopolita causada por nemátodos del género Toxocara. Los perros son hospedadores definitivos de Toxocara canis y pueden ser asintomáticos o presentar signos clínicos inespecíficos. El ser humano puede infectarse y desarrollar diferentes patologías.
En Costa Rica, se ha realizado estudios de prevalencia de huevecillos de Toxocara spp. en muestras de suelo y heces de caninos, pero no se ha investigado la prevalencia de anticuerpos contra este parásito en perros. Este estudio tiene como objetivo analizar 55 sueros de caninos de una comunidad periurbana de Heredia, Costa Rica, utilizando una prueba comercial para la detección de anticuerpos IgG anti-Toxocara spp. Además, se utilizó la información obtenida, mediante un cuestionario aplicado a las personas poseedoras de los perros, para conocer las prácticas de manejo con sus mascotas y el conocimiento sobre enfermedades zoonóticas.
Se determinó una seroprevalencia de 29%, lo cual evidencia que los caninos se infectaron con este parásito en alguna etapa de su vida. Se comprueba un desconocimiento generalizado acerca de las enfermedades zoonóticas por parte de los propietarios de los caninos; la mayoría de ellos aplicaba prácticas de manejo inadecuadas, tales como: no recoger las heces de sus perros en sitios públicos, poca o ninguna atención veterinaria para sus mascotas y protocolos de desparasitación de sus animales sin guía profesional ni registros confiables, lo cual podría favorecer la infección de sus mascotas con parásitos zoonóticos.
Toxocara canis larvae invade various tissues of different vertebrate species without developing into adults in paratenic host. The long-term survival of the larvae despite exposure to the well-armed immune response is a notable achievement. The larvae modulate the immune response to help the survival of both the host and the larvae. They skew the immune response to type 2/regulatory phenotype. The outstanding ability of the larvae to modulate the host immune response and to evade the immune arms is attributed to the secretion of Toxocara excretory-secretory products (TESPs). TESPs are complex mixture of differing molecules. The present review deals with the molecular composition of the TESPs, their interaction with the host molecules, their effect on the innate immune response, the receptor recognition, the downstream signals the adaptive immunity and the repair of tissues. This review also addresses the role of TESPs molecules in the immune evasion strategy and the potential effect of the induced immunomodulation in some diseases. Identification of parasite components that influence the nematode-host interactions could enhance understanding the molecular basis of nematode pathogenicity. Furthermore, the identification of helminths molecules with immunomodulatory potential could be used in immunotherapies for some diseases.
