Parasite Components Research Articles

Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis.

Scavenger receptors participate in a wide range of biological functions after binding to multiple non-self or altered self-ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial-associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.

A high-temperature high-pressure supercapacitor based on ionic liquids for harsh environment applications

The study of energy storage devices able to work in harsh environments is becoming of paramount importance. Numerous applications require devices able to sustain extreme temperatures but often the pressure is discarded. Herein we present the evaluation of the energy storage performance of a prototype electrochemical supercapacitor from room temperature and ambient pressure up to 170 °C and 640 bar. The supercapacitor is fabricated by exploiting activated carbon-based electrodes and an ionic liquid as electrolyte. [PYR14][TFSI] has been selected for this scope since it possesses suitable features for the investigated case of study. The whole device was sealed in a vacuum pouch and tested into a customized high-temperature high-pressure (HTHP) test bench. The device shows typical EDLC behavior in the whole HTHP region with capacitive response ranging from the low value of 46.4 mF cm−2 at {RT, 600 bar} up to 84.6 mF cm−2 at {175 °C, 640 bar}, with a reference value of 58.8 mF cm−2. At these points, the rated energy values are 92.8 mWh cm−2 and 169.1 mWh cm−2. We observed that pressure mainly acts on dissipative parasite components of the device while temperature strongly impinges transport properties and capacitance as expected from literature results.

Ex-vivo efficacy of commercially available anthelmintics against blood feeding stomach worm Haemonchus contortus of ruminants.

Haemonchus contortus is the most prevalent and pathogenic gastrointestinal nematodes (GINs) in ruminants causing extensive economic losses. It is essential to estimate the efficacy of common commercially available anthelmintics against Haemonchus contortus parasite. Here, we standardized an ex-vivo culture platform for H. contortus and evaluated the efficacy of commonly used anthelmintics namely, albendazole (ABZ), levamisole (LVM), ivermectin (IVM), closantel (CLS) and rafoxanide (RFX). Adult worms were collected from abomasa of slaughtered animals, cultured in MEM, DMEM, M199 or RPMI with or without 20% FBS for up to 72h. Cultured worms were incubated with ABZ, LVM, IVM, RFX or CLS in DMEM supplemented with 20% FBS at different concentrations (0.5-50µg/ml) in triplicates and examined at 0, 3, 6, 12, 24, 36 and 48h post treatment. Of the culture conditions, DMEM supplemented with 20% FBS supported the survival of H. contortus for (P < 0.001) longer period of time which was used in the evaluation of anthelmintics. The efficacy of CLS and RFX were significantly (P < 0.001) higher than other drugs and 100% mortality was observed at 2µg/ml of CLS and RFX within 12h post treatment. However, ABZ, LVM, and IVM showed significant effect at the concentration of 50µg/ml with 48, 36, and 24h, respectively. Morphological changes included severe cuticle disruption around the buccal cavity, posterior region and vulva as well as loss of cuticle structure integrity coupled with expulsion and fragmentation of digestive components of parasites when treated with 50µg/ml of ABZ, LVM, and IVM and 2µg/ml of RFX and CLS. Collectively, DMEM supplemented with 20% FBS can be used as ex-vivo culture platform for maintenance of H. contortus, and RFX and CLS can be used as the promising drugs for the prevention, control and treatment of H. contortus infections.

Precise Modeling for Reducing Output Voltage Control Error of RX-Sensorless IPT System

This paper presents RX-Sensorless technologies required in a self-induced type of low power wireless power transfer system. Recently, apart from the fields of smartphone and electrical vehicles which have been arduously studied for application of wireless power transfer, wireless power transfer technologies are being applied to various fields. Among them, there is a very rapidly increasing demand for low power systems in displays, body implant medical devices, drones, electrical kickboards and so on. In order to acquire portability of RX side of low power systems, the most critical factors are power density and efficiency. For this purpose, there have been very much ongoing studies to improve the power density on the RX side. Among various research, most frequently used types of methods involve derivation of output voltage using the physical quantity on the TX side while removing sensors on the RX side. However, in the modeling process to derive output voltage, they fail to properly reflect the parasite components of wireless power transfer and also due to the lack of measures in case of being out of the range of resonance frequency, there tends to be a high error in the output voltage which raises an issue. Therefore, this paper aims to suggest a model which reflects the parasite resistance components and the permeability rate of medium for the TX/RX pads of wireless power transfer systems. By reflecting winding losses and eddy current losses of TX/RX pads to a model, it is possible to reflect the parasite resistance components and using the Neumann formula, it is possible to reflect it to the medium between RX/TX pads. As a result, based on the derived model, it is possible to control the output voltage. Prototypes of hardware are designed and implemented for verifications. According to the computer simulation results and test results, output voltage estimates yield an error in the range of less than or equal to 8% and model-based output voltage control also shows the control range with errors of less than or equal to 5%.

Generation of red blood cells from stem cells: Achievements, opportunities and perspectives for malaria research.

Parasites of the genus Plasmodium that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell. As obligate, intracellular parasites, interactions between parasite and host red blood cell components are crucial to multiple aspects of the blood stage malaria parasite lifecycle. The requirement for, and involvement of, an array of red blood cell proteins in parasite invasion and intracellular development is well established. Nevertheless, detailed mechanistic understanding of host cell protein contributions to these processes are hampered by the genetic intractability of the anucleate red blood cell. The advent of stem cell technology and more specifically development of methods that recapitulate in vitro the process of red blood cell development known as erythropoiesis has enabled the generation of erythroid cell stages previously inaccessible in large numbers for malaria studies. What is more, the capacity for genetic manipulation of nucleated erythroid precursors that can be differentiated to generate modified red blood cells has opened new horizons for malaria research. This review summarises current methodologies that harness in vitro erythroid differentiation of stem cells for generation of cells that are susceptible to malaria parasite invasion; discusses existing and emerging approaches to generate novel red blood cell phenotypes and explores the exciting potential of in vitro derived red blood cells for improved understanding the broad role of host red blood cell proteins in malaria pathogenesis.

Macrophage Gal/GalNAc lectin 2 (MGL2)+ peritoneal antigen presenting cells during Fasciola hepatica infection are essential for regulatory T cell induction

Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.

Excreted secreted products from the parasitic nematode Steinernema carpocapsae manipulate the Drosophila melanogaster immune response

Steinernema carpocapsae is an entomopathogenic nematode (EPN) that rapidly infects and kills a wide range of insect hosts and has been linked to host immunosuppression during the initial stages of infection. The lethal nature of S. carpocapsae infections has previously been credited to its symbiotic bacteria; however, it has become evident that the nematodes are able to effectively kill their hosts independently through their excretion/secretion products (ESPs). Here we examined how the adult Drosophila melanogaster immune system is modulated in response to S. carpocapsae ESPs in an attempt to ascertain individual pathogenic contributions of the isolated compound. We found that the S. carpocapsae ESPs decrease the survival of D. melanogaster adult flies, they induce the expression of certain antimicrobial peptide-encoding genes, and they cause significant reduction in phenoloxidase enzyme activity and delay in the melanization response in males flies. We also report that S. carpocapsae ESPs affect hemocyte numbers in both male and female individuals. Our results indicate the manipulative role of EPN ESPs and reveal sex-specific differences in the host response against nematode infection factors. These findings are beneficial as they promote our understanding of the molecular basis of nematode pathogenicity and the parasite components that influence nematode-host interactions.

Case series on congenital malaria from a tertiary care hospital in North Eastern India

Malaria in early life is due to transfer of parasitized maternal red blood cell across placenta or direct transfer of parasite from placental syncytotrophoblast. Congenital malaria is defined as malaria acquired from mother in prenatal or perinatal period. Most of the cases in endemic area, passive transfer of high amount of maternal IgG antibody binds to malarial antigen and various components of parasites giving rise to various atypical clinical presentation. This case series will help neonatologist to think malaria in all non-specific symptoms of inconsolable cry, poor feeding, lethargy, even persistence of physiological jaundice. Very few reports of congenital malaria from India is reported in literature. Our series of five cases will address these few atypical symptoms.

Changing our view of the Schistosoma granuloma to an ecological standpoint.

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

Aspergillus niger trehalase enzyme induced morphological and protein alterations on Acanthamoeba cyst and molecular docking studies.

The cytotoxicity of Acanthamoeba is yet to fully illustrate due to recalcitrant of Acanthamoeba during cyst stage. The formation of the trehalose layer at the cyst stage protects the inner components of this opportunist protozoan parasite. Trehalase from the Aspergillus niger (AnTre) activity on the cyst of Acanthamoeba was determined based on AnTre dose-response, morphological and protein changes. The interaction of the AnTre and trehalose was also visualized through docking simulation. Vacuolation of the cyst can be seen when observed under light microscopy. Membrane integrity assessment suggested possible hydrolization of the AnTre enzyme to trehalose membranes which based on acridine orange and propidium iodide staining. Surface morphology based on scanning electron microscopy revealed the formation of bulging structure that was also proved through cross sectioning observed by transmission electron microscopy. Loss of internal structure of the cysts was clearly observed. Other morphological distinction where loss of rigid shape due to the destruction of the endo- and ecto cyst layers. However, the protein profile exhibits change of trehalose layer as responses to AnTre treatment. The observed biological results were also supported by interaction simulation based on molecular docking between trehalose and AnTre enzyme. In conclusion, this enzymatic approach could be developed into selective and effective mechanism to control Acanthamoeba without affecting the host especially mammals due to the absence of trehalose elements in the tissues of mammals.

Cloning, high-level gene expression and bioinformatics analysis of SP15 and LeIF from Leishmania major and Iranian Phlebotomus papatasi saliva as single and novel fusion proteins: a potential vaccine candidate against leishmaniasis.

Early exacerbation of cutaneous leishmaniasis is mainly affected by both the salivary and Leishmania parasite components. Little is known of the vaccine combination made by immunogenic proteins of sandfly saliva (SP15) with Leishmania parasites (LeIF) as a single prophylactic vaccine, namely SaLeish. Also, there are no data available to determine the species-specific sequence of SP15 isolated from the Iranian Phlebotomus papatasi. Integrated bioinformatics and genetic engineering methods were employed to design, optimize and obtain a vector-parasite-based vaccine formulation in a whole-length fusion form of LeIF-SP15 against leishmaniasis. Holistic gene optimization was initially performed to obtain a high yield of pure 'whole-SaLeish' expression using bioinformatics analyses. Genomic and salivary gland RNAs of wild-caught P. papatasi were extracted and their complementary DNA was amplified and cloned into pJET vector. The new chimeric protein of whole-SaLeish and randomly selected transcripts of native PpIRSP15 (GenBank accession nos. MT025054 and MN938854, MN938855 and MN938856) were successfully expressed, purified and validated by immunoblotting assay. Furthermore, despite the single amino acid polymorphisms of PpIRSP15 found at positions Y23 and E73 within the population of wild Iranian sandflies, antigenicity and conservancy of PpIRSP15 epitopes remained constant to activate T cells. The SaLeish vaccine strategy takes advantage of a plethora of vector-parasite immunogenic proteins with potential protective efficacy to stimulate both the innate and specific cellular immune responses against Leishmania parasites.

Linking murine resistance to secondary cystic echinococcosis with antibody responses targeting Echinococcus granulosus tegumental antigens.

Successful establishment of a parasite infection depends partially on the host intrinsic susceptibility to the pathogen. In cystic echinococcosis (CE), a zoonotic disease caused by the cestode parasite Echinococcus granulosus, the infection outcome in the murine model of secondary CE varies according to the mouse strain used. In this regard, intrinsic differences in susceptibility to the infection were previously reported for Balb/c and C57Bl/6 mice, being C57Bl/6 animals less permissive to secondary CE. Induction of parasite-specific antibodies has been suggested to play relevant roles in such susceptibility/resistance phenomena. Here, we report an in deep comparison of antibody responses induced in both mouse strains. Firstly, only C57Bl/6 mice were shown to induce specific-antibodies with efficient anti-parasite activities during early secondary CE. Then, through ImmunoTEM and Serological Proteome Analysis (SERPA), an evaluation of specific antibody responses targeting parasite tegumental antigens was performed. Both strategies showed that infected C57Bl/6 mice -unlike Balb/c animals- narrowed their IgG recognition repertoire against tegumental antigens, targeting fewer but potentially more relevant parasite components. In this sense, tegumental antigens recognition between Balb/c and C57Bl/6 mice, either by natural and/or induced antibodies, was analyzed through SERPA and MALDI-TOF/TOF studies. A total of 13 differentially recognized proteins (DRPs) uniquely targeted by antibodies from C57Bl/6 mice were successfully identified, wherein a subset of 7 DRPs were only recognized by infection-induced antibodies, suggesting their potential as natural protective antigens. In this regard, immunoinformatic analyses showed that such DRPs exhibited higher numbers of possible T cell epitopes towards the H-2-IAb haplotype, which is present in C57Bl/6 mice but absent in Balb/c animals. In summary, our results showed that the genetic predisposition to generate better T-dependent antibody responses against particular tegumental antigens might be a key factor influencing host susceptibility in the murine model of secondary CE.

Inorganic ions on hemozoin surface provide a glimpse into Plasmodium biology

In malaria, Plasmodium parasites produce hemozoin (Hz) as a route to detoxify free heme released from the catabolism of hemoglobin. Hz isolated from the parasites is encapsulated in an organic layer constituted by parasite and host components. This organic coating may play a role in Hz formation and in the immunomodulatory properties attributed to Hz, and they may influence the mode of action of antimalarials that block Hz formation. In this work, we analyze the organic layer adhered to Hz, and find Na, Cl, Si, Ca and P present, in addition to organic material. Our results suggest that Na, Cl, and P adsorb during Hz release from the red blood cells, while Si and Ca derive from components present during Hz biomineralization within the digestive vacuole of the parasite. Overall, we show that inorganic elements associated with Hz surface provide insights into the biological functions of Plasmodium parasites.

C57BL/6 mice immunized with synthetic peptides from Toxoplasma gondii surface and microneme immunodominant antigens are able to decrease parasite burden in the brain tissues

Toxoplasmosis is a disease caused by Toxoplasma gondii, an intracellular protozoan able to infect a wide range of hosts. The infection is particularly severe in immunocompromised patients or during pregnancy, circumstances in which the parasite could find a more favorable microenvironment to replicate and invade host tissues. The current treatment consists in toxic drugs for the patients, being not appropriate for the fetuses and immunodeficient patients. So far, there is a lack of available vaccine to prevent the disease. The present study aimed to evaluate the immune response induced by peptides derived from parasite immunodominant proteins from key components, as surface, rhoptry, microneme and dense granule antigens. A panel of eleven peptides was selected considering the highest scores for B cell epitope prediction by in silico analyses. The peptides were divided in groups, according to the parasite organelle locations, and used to immunize C57BL/6 mice. The animals were submitted to three doses of immunization and infected by 10 cysts of T. gondii ME49 strain. Blood samples were collected and used to measure the production of antibodies and cytokines, while the brains were collected to determine the parasite burden by quantitative polymerase chain reaction (qPCR). It was found that synthetic peptides from all targets were able to induce IgG synthesis in immunized mice, as well as to modulate the Th1/Th2 cytokine production, particularly the MIC and SRS groups, which presented the IFN-γ/IL-10 and TNF-α/IL-10 ratios 30 and 10 times higher, respectively, when compared with non-immunized group. Interestingly, the animals from MIC and SRS groups had significantly lower levels of T. gondii DNA in their brains. In summary, it can be concluded that peptides mainly from SRS and MIC parasite components constitute relevant targets to design vaccine candidates against parasite burden observed during chronic toxoplasmosis.

The Entamoeba histolytica Syf1 Homolog Is Involved in the Splicing of AG-Dependent and AG-Independent Transcripts.

Syf1 is a tetratricopeptide repeat (TPR) protein implicated in transcription elongation, spliceosome conformation, mRNA nuclear-cytoplasmic export and transcription-coupled DNA repair. Recently, we identified the spliceosomal components of the human parasite Entamoeba histolytica, among them is EhSyf. Molecular predictions confirmed that EhSyf contains 15 type 1 TPR tandem α-antiparallel array motifs. Amoeba transformants carrying plasmids overexpressing HA-tagged or EhSyf silencing plasmids were established to monitor the impact of EhSyf on the splicing of several test Entamoeba transcripts. EhSyf Entamoeba transformants efficiently silenced or overexpressed the proteins in the nucleus. The overexpression or absence of EhSyf notably enhanced or blocked splicing of transcripts irrespective of the strength of their 3′ splice site. Finally, the absence of EhSyf negatively affected the transcription of an intron-less transcript. Altogether our data suggest that EhSyf is a bona fide Syf1 ortholog involved in transcription and splicing.

Does host-absent vocalisation of common cuckoo chicks increase hosts’ food provisioning behaviour?

Parent-absent vocalisation is produced by nestlings of several bird families when the parents are away from the nest. An analogous behaviour, host-absent vocalisation, has been found in some species of avian brood parasites and there are several explanations why this behaviour could have evolved. Using playback experiments, we examined whether polygynous great reed warblers (Acrocephalus arundinaceus) adjust their food provisioning behaviour in response to host-absent begging vocalisation uttered by the common cuckoo (Cuculus canorus) chicks. We found that both on monogamous and polygynous nests, host pair members responded to the broadcasted parasite begging signals by increasing their feeding rates; yet, they did not deliver larger volumes of food as a consequence of somewhat smaller prey brought per visit. Nevertheless, we propose that host-absent vocalisation of the common cuckoo chick may still represent a signal of hunger that may compensate for other, deficient components of parasite begging display. However, the efficiency of this signal may be limited by the foster parents’ provisioning abilities and local prey availability. Bird chicks beg loudly for food when their parents are at the nest, as well as when the parents search for food elsewhere. The same applies to young parasites raised by their hosts. Experimental playback of host-absent begging calls of cuckoo chicks increased great reed warbler feeding frequency but had no effect on the volume of food delivered. Host-absent vocalisation may represent signal of hunger; however, its effectiveness may be limited by provisioning abilities of the hosts.

Extracellular Vesicles in Chagas Disease: A New Passenger for an Old Disease.

Extracellular vesicles (EVs) are small lipid vesicles released by prokaryotic and eukaryotic cells containing nucleic acids, proteins, and small metabolites essential for cellular communication. Depending on the targeted cell, EVs can act either locally or in distant tissues in a paracrine or endocrine cell signaling manner. Released EVs from virus-infected cells, bacteria, fungi, or parasites have been demonstrated to perform a pivotal role in a myriad of biochemical changes occurring in the host and pathogen, including the modulation the immune system. In the past few years, the biology of Trypanosoma cruzi EVs, as well as their role in innate immunity evasion, has been started to be unveiled. This review article will present findings on and provide a coherent understanding of the currently known mechanisms of action of T. cruzi-EVs and hypothesize the implication of these parasite components during the acute and chronic phases of Chagas disease.

Genetic ancestry effects on the distribution of toll-like receptors (TLRs) gene polymorphisms in a population of the Atlantic Forest, São Paulo, Brazil

The innate immune system governed by toll-like receptors (TLRs) provides the first line of defense against pathogens. Surface-localized TLR1 and TLR6 are known to detect parasite components. TLR encoding genes were shown to display signatures of recent positive selection in Europeans and might be involved in local adaptation at immune-related genes. To verify the influence of Brazilian population admixture on the distribution of polymorphisms in TLRs, we analyzed the genotype frequencies of 24 polymorphisms distributed across five TLR genes in a Southeastern Brazilian population where autochthonous cases of malaria occur in small foci of transmission. The estimation of ancestry showed mainly European ancestry (63%) followed by African ancestry (22%). Mean proportions of European ancestry differed significantly between the genotypes of the TLR1 (I602S) gene and in the TLR6 (P249S) gene. The chance of having the G allele in TLR1 gene increases as European ancestry increases as well as the chance of having the T allele in the TLR6 gene. The 602S allele is related to a ‘‘hypo-responsiveness’’ possibly explaining the high prevalence of asymptomatic malaria cases in areas of Southeastern Brazil. Our results underline the necessity to include informative ancestry markers in genetic association studies in order to avoid biased results.

Fasciola hepatica Immune Regulates CD11c+ Cells by Interacting with the Macrophage Gal/GalNAc Lectin.

Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a trematode zoonosis of interest in public health and livestock production. Like other helminths, F. hepatica modulates the host immune response by inducing potent polarized Th2 and regulatory T cell immune responses and by downregulating the production of Th1 cytokines. In this work, we show that F. hepatica glycans increase Th2 immune responses by immunomodulating TLR-induced maturation and function of dendritic cells (DCs). This process was mediated by the macrophage Gal/GalNAc lectin (MGL) expressed on DCs, which recognizes the Tn antigen (GalNAc-Ser/Thr) on parasite components. More interestingly, we identified MGL-expressing CD11c+ cells in infected animals and showed that these cells are recruited both to the peritoneum and the liver upon F. hepatica infection. These cells express the regulatory cytokines IL-10, TNFα and TGFβ and a variety of regulatory markers. Furthermore, MGL+ CD11c+ cells expand parasite-specific Th2/regulatory cells and suppress Th1 polarization. The results presented here suggest a potential role of MGL in the immunomodulation of DCs induced by F. hepatica and contribute to a better understanding of the molecular and immunoregulatory mechanisms induced by this parasite.

Prospects for vaccination against pathogenic African trypanosomes

African trypanosomes cause human and animal African trypanosomiases, which are chronic, debilitating and often fatal diseases of people and livestock in sub-Saharan Africa. The extracellular protozoan parasites are exemplars of antigenic variation. They direct host-protective B-cell and T-cell immune responses towards hypervariable components of their variable surface glycoprotein coat and evade immune elimination by generating new surface coat antigenic variants at a rate that supersedes immune destruction. This results in recurring waves of parasitemia, tissue invasion and escalating immunopathology in trypanosomiasis-susceptible hosts. Here, we discuss the possibility that host control of African trypanosomes might be improved by immunization with conserved VSG peptides and invariant surface glycoproteins. Infection-induced T-cell recall responses to these typically poorly expressed or nonimmunogenic parasite components induce tissue phagocytes to produce microbicidal materials that kill trypanosomes. Preliminary data that support this immune-enhancing vaccine strategy are discussed, as are host and parasite interactions that might downregulate the protective responses. These include infection-induced immunosuppression and increasing virulence of infecting parasites over time.