Trypanosoma cruzi, the etiological agent of Chagas disease, releases factors, including antigens from the trans-sialidase (TS) superfamily, which modulate the host immune responses. Tc13 antigens belong to group IV of TSs and are characterized by C-terminal EPKSA repeats. Here, we studied the effect of the Tc13 antigen from the Tulahuén strain, Tc13Tul, on primary cultures of splenocytes from naïve BALB/c mice. Recombinant Tc13Tul increased the percentage of viable cells and induced B (CD19+) lymphocyte proliferation. Tc13Tul stimulation also induced secretion of non-specific IgM and interferon-γ (IFN-γ). The same effects were induced by Tc13Tul on splenocytes from naïve C3H/HeJ mice. In vivo administration of Tc13Tul to naïve BALB/c mice increased non-specific IgG in sera. In addition, in vitro cultured splenocytes from Tc13Tul-inoculated mice secreted a higher basal level of non-specific IgM than controls and the in vitro Tc13Tul stimulation of these cells showed an enhanced effect on IgM and IFN-γ secretion. Our results indicate that Tc13Tul may participate in the early immunity in T. cruzi infection by favouring immune system evasion through B-cell activation and non-specific Ig secretion. In contrast, as IFN-γ is an important factor involved in T. cruzi resistance, this may be considered a Tc13Tul effect in favour of the host.

Obligately intracellular microsporidia regulate their host cell life cycles, including apoptosis, but this has not been evaluated in phagocytic host cells such as macrophages that can facilitate infection but also can be activated to kill microsporidia. We examined two biologically dissimilar human-infecting microsporidia species, Encephalitozoon cuniculi and Vittaforma corneae, for their effects on staurosporine-induced apoptosis in the human macrophage-differentiated cell line, THP1. Apoptosis was measured after exposure of THP-1 cells to live and dead mature organisms via direct fluorometric measurement of Caspase 3, colorimetric and fluorometric TUNEL assays, and mRNA gene expression profiles using Apoptosis RT2 Profiler PCR Array. Both species of microsporidia modulated the intrinsic apoptosis pathway. In particular, live E. cuniculi spores inhibited staurosporine-induced apoptosis as well as suppressed pro-apoptosis genes and upregulated anti-apoptosis genes more broadly than V. corneae. Exposure to dead spores induced an opposite effect. Vittaforma corneae, however, also induced inflammasome activation via Caspases 1 and 4. Of the 84 apoptosis-related genes assayed, 42 (i.e. 23 pro-apoptosis, nine anti-apoptosis, and 10 regulatory) genes were more affected including those encoding members of the Bcl2 family, caspases and their regulators, and members of the tumour necrosis factor (TNF)/TNF receptor R superfamily.

Despite the profound health implications of Necator americanus infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae trigger ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs.

A serine protease-like enzyme found in detergent extracts of Schistosoma mansoni adult worms perfused from infected mice has been purified from mouse blood and further characterized. The enzyme is approximately 85 kDa and hydrolyses N-acetyl-DL-phenylalanine β-naphthyl–ester, a chromogenic substrate for chymotrypsin-like enzymes. The enzyme from S. mansoni worms appears to be antigenically and enzymatically similar to a molecule that is present in normal mouse blood and so is seemingly host-derived. The enzyme was partially purified by depleting normal mouse serum of albumin using sodium chloride and cold ethanol, followed by repeated rounds of purification by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified material was subjected to tandem mass spectrometry and its derived peptides found to belong to mouse carboxylesterase 1C. Its ability to hydrolyse α- or β-naphthyl acetates, which are general esterase substrates, has been confirmed. A similar carboxylesterase was purified and characterized from rat blood. Additional evidence to support identification of the enzyme as a carboxylesterase has been provided. Possible roles of the enzyme in the mouse host–parasite relationship could be to ease the passage of worms through the host's blood vessels and/or in immune evasion.

The Apicomplexa is a phylum of parasitic protozoa, which includes the malaria parasite Plasmodium, amongst other species that can devastate human and animal health. The past decade has seen the release of genome sequences for many of the most important apicomplexan species, providing an excellent basis for improving our understanding of their biology. One of the key features of each genome is a unique set of large, variant gene families. Although closely related species share the same families, even different types of malaria parasite have distinct families. In some species they tend to be found at the ends of chromosomes, which may facilitate aspects of gene expression regulation and generation of sequence diversity. In others they are scattered apparently randomly across chromosomes. For some families there is evidence they are involved in antigenic variation, immune regulation and immune evasion. For others there are no known functions. Even where function is unknown these families are most often predicted to be exposed to the host, contain much sequence diversity and evolve rapidly. Based on these properties it is clear that they are at the forefront of host–parasite interactions. In this review I compare and contrast the genomic context, gene structure, gene expression, protein localization and function of these families across different species.

Bovine herpesvirus 1 (BHV-1) causes a variety of diseases and is globally distributed. It infects via mucosal epithelium, leading to rapid lytic replication and latent infection, primarily in sensory ganglia. Large amounts of virus can be excreted by the host on primary infection or upon recrudescence of latent infection, resulting in disease spread. The bovine immune response to BHV-1 is rapid, robust, balanced, and long-lasting. The innate immune system is the first to respond to the infection, with type I interferons (IFNs), inflammatory cytokines, killing of infected host cells, and priming of a balanced adaptive immune response. The virus possesses a variety of immune evasion strategies, including inhibition of type I IFN production, chemokine and complement binding, infection of macrophages and neutrophils, and latency. BHV-1 immune suppression contributes to the severity of its disease manifestations and to the bovine respiratory disease complex, the leading cause of cattle death loss in the USA.

Pentastomids comprise a highly specialized taxon of arthropod-like parasites that probably became adapted to the lungs of amphibians and reptiles early in their long evolutionary history. Few other macroparasites exploit this particular niche. Pentastomids are often large, long-lived and yet they cause little observable pathology in lungs, despite being haematophagous. The lungs of all tetrapods are lined with pulmonary surfactant, a remarkable biological material consisting of a complex mixture of phospholipids, neutral lipids and proteins that has the unique ability to disperse over the air-liquid lining of the lung. In the lower tetrapods it acts as an anti-glue preventing adhesion of respiratory surfaces when lungs collapse during swallowing prey or upon expiration. In mammals, pulmonary surfactant also plays a critical role regulating the activity of alveolar macrophages, the predominant phagocytes of the lower airways and alveoli. This review outlines the evidence suggesting that lung-dwelling pentastomids, and also nymphs encysted in the tissues of mammalian intermediate hosts, evade immune surveillance and reduce inflammation by coating the chitinous cuticle with a their own stage-specific surfactant. The lipid composition of surfactant derived from lung instars of the pentastomid Porocephalus crotali cultured in vitro is very similar to that recovered from the lung of its snake host. Pentastomid surfactant, visualised as lamellate droplets within sub-parietal cells, is delivered to the cuticle via chitin-lined efferent ducts that erupt at a surface density of < 400 mm-2. The fidelity of the system, which ensures that every part of the cuticle surface is membrane-coated, testifies to its strategic importance. Two other extensive glands discharge membrane-associated (hydrophobic ?) proteins onto the hooks and head; some have been purified and partly characterized but their role in minimising inflammatory responses is, as yet, undetermined.

The excretory–secretory antigen of Fasciola hepatica (ESA) is involved in the suppressive phenomena of cellular immune responses in rats. The ESA can depress the proliferative response of spleen mononuclear cells and inhibit nitric oxide (NO) production by peritoneal cells. In the present study we identified ESA proteins of ca 24 kDa, which shared significant sequence homology to glutathione-S-transferase (GST) obtained from homogenates of F. hepatica adults, other helminths and different mammals. When the dimeric form of these proteins ca 48 kDa was cultured with rat spleen cells, a significant decrease of proliferative response to Con A was detected, starting from 20 μg/ml of ESA protein (P<0·03). We also observed a significant inhibition of nitrite production by incubation with the dimeric form in normal peritoneal macrophages (P<0·04). These results indicated that the GST secreted by the parasite could be involved in evasion of the parasite from the host immune response.

Infection by a variety of species of intestinal nematode infection gives rise to a wide variation in parasite load within a host population. There has been much investigation into the basis of this variation and is thought to involve several factors. Studies of infections of gut dwelling nematodes in laboratory rodents has clearly demonstrated that this variation may be due to the production of cytokines produced as part of the host immune response to infection. More specifically, activation of distinct T helper cell subsets leads to the generation of effective or ineffective responses resulting in clearance of the parasite load or maintenance of chronic infection. The induction of differential responses remains to be determined but is likely to be influenced at a number of levels including involvement of accessory cells and activation of co-stimulatory molecules on antigen presenting cells. Moreover, it appears that these parasites may actively interfere with the host cytokine response to promote their own survival. This review concentrates on recent findings of cytokine mediated control of intestinal nematodes highlighting a central role for the immune system in regulating both acute and chronic infection by these parasites.

The modern biology era in which molecular analyses dominate and immunology, cell biology and molecular genetics are prominent, has created unprecedented opportunities for the vaccine developer. The need for new and improved vaccines against many infectious disease agents is also great, no more so than for the protozoan and helminth parasite scourges of the rural poor in the tropical, less-industrially developed world. Despite the opportunities and needs, no vaccine against any human parasite yet exists nor does any molecular vaccine against any parasite; this chapter is a general discussion on the reasons for this state of affairs that assuredly will change soon.

Glycans at the surface of adult Schistosoma mansoni were investigated with gold-labelled lectins. The fragile complex of the glycans with the outer membranes could be preserved for electron microscopy by avoiding extensive pre-fixation with aldehydes and by introducing osmium-ferrocyanide as a membrane fixative. Male and female worms were entirely covered with glycans that intensely bound lectins from Erythrina cristagalli and Datura stramonium, suggesting that galactose(β1–4)N-acetylglucosamine residues occur in high numbers in the surface glycans. Similar staining was obtained with lectins from Triticum vulgaris, Glycine max and Ricinus communis agglutinin I, which react with N-acetylglucosamine or terminal galactose residues and bind non-selectively with high affinity to N-acetyllactosamine. Fucose, N-acetylgalactose and sialic acid were not detected with lectins and sialidase treatment. The tegument contained an abundance of glycans with the same lectin reactivities as the surface-expressed molecules, indicating that the worms synthesize and replenish their surface glycans and do not merely adsorb host substances. Glycomimesis is discussed as a mechanism of immune evasion in view of N-acetyllactosamine being a common and weakly immunogenic component in glycans of vertebrate hosts. S. mansoni might disguise themselves with the glycans against attack by immune effectors.

Bovine respiratory tract disease is a multi-factorial disease complex involving several viruses and bacteria. Viruses that play prominent roles in causing the bovine respiratory disease complex include bovine herpesvirus-1, bovine respiratory syncytial virus, bovine viral diarrhea virus and parinfluenza-3 virus. Bacteria that play prominent roles in this disease complex are Mannheimia haemolytica and Mycoplasma bovis. Other bacteria that infect the bovine respiratory tract of cattle are Histophilus (Haemophilus) somni and Pasteurella multocida. Frequently, severe respiratory tract disease in cattle is associated with concurrent infections of these pathogens. Like other pathogens, the viral and bacterial pathogens of this disease complex have co-evolved with their hosts over millions of years. As much as the hosts have diversified and fine-tuned the components of their immune system, the pathogens have also evolved diverse and sophisticated strategies to evade the host immune responses. These pathogens have developed intricate mechanisms to thwart both the innate and adaptive arms of the immune responses of their hosts. This review presents an overview of the strategies by which the pathogens suppress host immune responses, as well as the strategies by which the pathogens modify themselves or their locations in the host to evade host immune responses. These immune evasion strategies likely contribute to the failure of currently-available vaccines to provide complete protection to cattle against these pathogens.

An enzyme found previously in extracts of adult Schistosoma mansoni worms, that hydrolysed the chromogenic substrate N-acetyl-DL-phenylalanine β-naphthyl-ester, has here been further investigated and characterized. Evidence that the molecule found in the parasite was antigenically and enzymatically homologous with a constituent of normal mouse plasma has been consolidated using a monospecific serum in immunoelectrophoresis and Western immunoblotting. The molecular size of the enzyme was found to be approximately 70 kDa and it was inhibited by a serine protease inhibitor, but not by inhibitors of other classes of protease. The enzymatic activity found in normal mouse serum was also found in normal rat serum, but not in sera from several other mammalian species.

Past and more recent research has examined the ultrastructure, metabolism, cell biology, genomics and post-genomics of schistosome schistosomula. These areas are considered and discussed in this review with particular emphasis on (1) the early migration phases through the host, (2) interaction of the host immune response with the parasite surface, (3) glucose uptake mechanisms, and (4) defining the transcriptional profiles of lung-stage schistosomula compared with other developmental stages using microarrays. The microarray profiling studies suggest caution is required when considering the use of schistosomes obtained by in vitro means for molecular or biochemical studies.

During infection, programmed cell death, i.e. apoptosis, is an important effector mechanism of innate and adaptive host responses to parasites. In addition, it fulfils essential functions in regulating host immunity and tissue homeostasis. Not surprisingly, however, adaptation of parasitic protozoa to their hosts also involves modulation or even exploitation of cell death in order to facilitate parasite survival in a hostile environment. During recent years, considerable progress has been made in our understanding of apoptosis during parasitic infections and there is now convincing evidence that apoptosis and its modulation by protozoan parasites has a major impact on the parasite-host interaction and on the pathogenesis of disease. This review updates our current knowledge on the diverse functions apoptosis may fulfil during infections with diverse protozoan parasites including apicomplexans, kinetoplastids and amoebae. Furthermore, we also summarize common mechanistic themes of the pro- and anti-apoptotic activities of protozoan parasites. The diverse and complex effects which parasitic protozoa exert on apoptotic cell death within the host highlight fascinating interactions of parasites and their hosts. Importantly, they also stress the importance of further investigations before the modulation of host cell apoptosis can be exploited to combat parasitic infections.

Vaccinia virus, a member of the Poxviridae, expresses many proteins involved in immune evasion. In this review, we present a brief characterisation of the virus and its effects on host cells and discuss representative secreted and intracellular proteins expressed by vaccinia virus that are involved in modulation of innate immunity. These proteins target different aspects of the innate response by binding cytokines and interferons, inhibiting cytokine synthesis, opposing apoptosis or interfering with different signalling pathways, including those triggered by interferons and toll-like receptors.

The effect of Sanguinicola inermis on serum antibody and complement activity in Cyprinus carpio was assessed using an ELISA and haemolytic assays. Possible immune evasion strategies were assessed using immunodetection of host proteins on the surface of the parasite. Carp acclimatized to 20 or 25 °C were infected by exposure to 500 cercariae or injected intraperitoneally with 150 cercariae, and serum monitored over a 63-day period. In cercariae-injected carp, irrespective of time and temperature, a significant increase occurred in complement activity being greatest at 25 °C. In addition, fish exposed to the cercariae of S. inermis and maintained at 20 °C the level of complement activity was significantly higher after 5 weeks compared to controls. At 20 °C intraperitoneal injections of parasites increased serum antibody levels which peaked after 7 days. In contrast, at 25 °C, antibody levels were maintained over 63 days. Exposure of fish to infection did not appear to stimulate antibody production. Immunofluorescence studies revealed ‘host-like’ molecules on the surface of the cercarial body exposed to carp serum and adult flukes obtained directly from the fish or cultured for 24 h in L15 medium. The possible role of ‘host-like’ molecules in immune evasion is discussed and the response at different temperatures is related to infection dynamics.

The Py235 merozoite rhoptry protein of the rodent malaria agent Plasmodium (yoelii) yoeli is encoded by the Py235 multigene family whose members are transcribed during the parasite's asexual life-cycle in a fashion where single schizonts subsequently give rise to sets of merozoites containing distinct Py235 transcripts. Homologues of Py235 are found in other malaria species, and antibodies to both Py235 and P. falciparum homologues inhibit merozoite invasion, suggesting a unique survival strategy involving immune evasion and host adaptation. Using a mathematical approach to model this free-living stage of Plasmodium in interaction with specific antibodies and a heterogeneous red blood cell population, we investigate if, and under what conditions, this mechanism of clonal phenotypic variation can play a role in immune evasion and adaptation to a dynamic erythropoietic environment.

Members of the genus Trichostrongylus, such as T. vitrinus, being endemic in Northern Europe, are among the principal causative nematodes which contribute to parasitic gastro-enteritis in sheep world-wide, inhabiting the proximal small intestine and causing damage to the mucosa. This results in impaired nutrient absorption as well as a pronounced inflammatory response with cellular infiltration of the mucosa, including a pronounced mast cell response. These mast cells release serine proteinases that enhance the passage of effector cells and macromolecules across epithelial boundaries and into direct contact with the invading parasite. The adult and larval stages of T. vitrinus release a number of serine proteinases in vitro that may contribute to tissue invasion and nutrient acquisition in vivo. This study describes the molecular cloning and characterization of a serine proteinase inhibitor (serpin)Sequence reported here is available with GenBank Accession number Y12233. that is present in extracts of all the parasitic stages, becoming more abundant as the life-cycle progresses. The serpin is present in the in vitro excretory/secretory products (ES) of 4th-stage larval and adult parasites, being more abundant in the former. The serpin was expressed in E. coli and the recombinant protein was a potent inhibitor of several host serine proteinases including mast cell proteinases. The serpin may regulate the activity of the parasite serine proteinases or it may modulate the host immune response to the parasite by inhibiting the activity of serine proteinases released from host inflammatory cells.

Killing of intramolluscan schistosomes by host haemocytes is mediated by reactive oxygen metabolites. Hence, defence against oxidative damage is essential for the parasite to survive. In this study, expression of three key antioxidant enzymes, superoxide dismutase (EC 1.15.1.1), glutathione peroxidase (EC 1.11.1.9) and glutathione-S-transferase (EC 2.5.1.18) was determined in Schistosoma mansoni miracidia, sporocysts and cercariae. Stage-dependent expression of these enzymes was shown to be regulated at the transcriptional level. Second, the influence on enzyme expression of reactive oxygen species (ROS) and of haemocytes from schistosome-resistant and -susceptible host snails was determined. Generation of ROS by xanthine/xanthine oxidase resulted in increased transcript levels for all three enzymes. Addition of hydrogen peroxide induced a significantly increased expression of GPx and SOD but not GST. Snail haemocytes induced an up-regulation of SOD and GPx at 12 and 18 h post-exposure, respectively. Susceptible haemocytes elicited a stronger induction of transcript expression than resistant haemocytes. After 36–48 h, SOD remained up-regulated in sporocysts encapsulated by haemocytes from susceptible hosts, whereas a down-regulation of SOD and GPx occurred in schistosomes encapsulated by haemocytes from resistant snails. These observations indicate that schistosomes express elevated levels of antioxidant enzymes in interaction with haemocytes from susceptible snail hosts in which they survive. On the other hand, haemocytes of resistant snails may interfere with reactive oxygen detoxification via down-regulation of schistosome antioxidant enzymes, thus shifting the balance towards parasite killing.