Spatially extended host-parasite interactions: the role of recovery and immunity

Techniques for determining the long-term dynamics of host-parasite systems are well established for mixed populations. The field of spatial modelling in ecology is more recent but a number of key advances have been made. In this paper, we use state-of-the-art approximation techniques, supported by simulations, in order to investigate the role of recovery and immunity in spatially structured populations. Our approach is to use correlation models, namely pair-wise models, to capture the spatial relationships of contacts and interactions between individuals. We use the pair-wise framework to address a number of key ecological questions; including, the persistence of endemic limit cycles and regions of parasite-driven extinction--features which differentiate spatial from non-spatial models--and the effects on invasion fitness. We demonstrate a loss of limit cycle behaviour, in addition to an increase in the critical transmissibility and extinction thresholds, when recovery is included. This approach allows for a better analytical understanding of the dynamics of host-parasite interactions and demonstrates the importance of recovery and immunity in local interactions.     

The cytoskeleton and motor proteins of human schistosomes and their roles in surface maintenance and host-parasite interactions

Schistosomes are parasitic blood flukes, responsible for significant human disease in tropical and developing nations. Here we review information on the organization of the cytoskeleton and associated motor proteins of schistosomes, with particular reference to the organization of the syncytial tegument, a unique cellular adaptation of these and other neodermatan flatworms. Extensive EST databases show that the molecular constituents of the cytoskeleton and associated molecular systems are likely to be similar to those of other eukaryotes, although there are potentially some molecules unique to schistosomes and platyhelminths. The biology of some components, particular those contributing to host-parasite interactions as well as chemotherapy and immunotherapy are discussed. Unresolved questions in relation to the structure and function of the tegument relate to dynamic organization of the syncytial layer.     

The role of mucins in host-parasite interactions: Part II - helminth parasites

Some parasites express mucin-like molecules. These have possible roles in attachment and invasion of host cells and in the avoidance of host immune processes. Enzymes of parasite origin might also facilitate infection, either by degrading host mucus barriers or by generating binding sites on host cells. Host mucins have roles in preventing parasite establishment or in parasite expulsion. They, in turn, might be exploited by parasites, either as sources of fuel or binding sites, or as host-finding targets. Here, we describe the biochemical properties of mucins and mucin-like molecules in relation to interactions (established and putative) between helminth parasites and their hosts.     

Dense-granule organelles of Toxoplasma gondii: their role in the host-parasite relationship

The dense-granule organelles of Toxoplasma gondii are secretory vesicles that play a major role in the structural modifications of the parasitophorous vacuole. In this article, Marie-France Cesbron-Delauw reviews work on a prominent set of molecules recently characterized as components of the dense granules, and discusses various aspects on their post-translational trafficking and delivery within the host cell.     

The role of mucins in host-parasite interactions. Part I-protozoan parasites

Parasite-derived mucin-like molecules might be involved in parasite attachment to and invasion of host cells. In addition, parasites might secrete mucin-degrading enzymes, enabling the penetration of protective mucus gels that overlie the mucosal surfaces of their potential hosts. Furthermore, they might generate binding ligands on the membrane-bound mucins of host cells by using specific glycosidases. It is possible that host mucins and mucin-like molecules prevent the establishment of parasites or facilitate parasite expulsion. They might also serve as a source of metabolic energy and adhesion ligands for those parasites adapted to exploit them. Sally Hicks and colleagues here review the biochemical properties of mucins and mucin-like molecules in relation to interactions (established and putative) between protozoan parasites and their hosts.     

Schistosomes: the road from host-parasite interactions to vaccines in clinical trials

Insights over recent years into the interactions between helminths, including schistosomes, and the immune system have generated new concepts in immunology and significant advances in vaccine strategies. Here, we report recent advances that substantially increase our understanding of the nature of the host innate and adaptive responses to schistosomes and on strategies elaborated by the parasite to manipulate such responses. We also describe the long road that has allowed us to move from the identification of an anti-schistosome vaccine candidate, a 28kDa glutathione-S-transferase, to its recent evaluation in human clinical trials.     

Chemokines in host-parasite interactions in leishmaniasis

Crucial to the defense against leishmaniasis is the ability of the host to mount a cell-mediated immune response capable of controlling and/or eliminating the parasite. Cell recruitment to the site of infection is essential to the development of the host cellular immune response. The process is controlled by chemokines, which are chemotactic cytokines produced by leukocytes and tissue cells.     

Coevolution: Mathematical analysis of host-parasite interactions

An SIS epidemic transmitted by two similar strains of parasite acting on a host population of three genotypes which differ in their reaction to the disease is modelled and analyzed. Singular perturbation techniques are used to reduce the original system of nine differential equations to a coupled system of two equations describing the slowtime coevolution of gene frequency and parasite strain frequency.Karen Christine Beck died June 25, 1983 at home.Born February 8, 1952 in Madison, Wisconsin, She received a B.A. degree in 1974 from Luther College, Decorah, Iowa and a Ph.D. in mathematics in 1980 from the University of Iowa. Since that time she has been an instructor in the Mathematics Department at the University of Utah. She was to become an Assistant Professor at the University of Texas, Arlington, beginning Autumn, 1983. Dr. Beck's areas of specialization in mathematics were Mathematical Analysis and Mathematical Biology. She published numerous research articles that resolved various problems in these areas.     

Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions

Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H(2)O(2), conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.     

Heterogeneous interspecific interactions in a host-parasite system

Macroparasites of vertebrates usually occur in multi-species communities, producing infections whose outcome in individual hosts or host populations may depend on the dynamics of interactions amongst the different component species. Within a single co-infection, competition can occur between conspecific and heterospecific parasite individuals, either directly or via the host's physiological and immune responses. We studied a natural single-host, multi-parasite model infection system (polystomes in the anuran Xenopus laevis victorianus) in which the parasite species show total interspecific competitive exclusion as adults in host individuals. Multi-species infection experiments indicated that competitive outcomes were dependent on infection species composition and strongly influenced by the intraspecific genetic identity of the interacting organisms. Our results also demonstrate the special importance of temporal heterogeneity (the sequence of infection by different species) in competition and co-existence between parasite species and predict that developmental plasticity in inferior competitors, and the induction of species-specific host resistance, will partition the within-host-individual habitat over time. We emphasise that such local (within-host) context-dependent processes are likely to be a fundamental determinant of population dynamics in multi-species parasite assemblages.     

Heads or tails: host-parasite interactions in the Drosophila-Wolbachia system

Wolbachia strains are endosymbiotic bacteria typically found in the reproductive tracts of arthropods. These bacteria manipulate host reproduction to ensure maternal transmission. They are usually transmitted vertically, so it has been predicted that they have evolved a mechanism to target the host's germ cells during development. Through cytological analysis we found that Wolbachia strains display various affinities for the germ line of Drosophila. Different Wolbachia strains show posterior, anterior, or cortical localization in Drosophila embryos, and this localization is congruent with the classification of the organisms based on the wsp (Wolbachia surface protein) gene sequence. This embryonic distribution pattern is established during early oogenesis and does not change until late stages of embryogenesis. The posterior and anterior localization of Wolbachia resembles that of oskar and bicoid mRNAs, respectively, which define the anterior-posterior axis in the Drosophila oocyte. By comparing the properties of a single Wolbachia strain in different host backgrounds and the properties of different Wolbachia strains in the same host background, we concluded that bacterial factors determine distribution, while bacterial density seems to be limited by the host. Possible implications concerning cytoplasmic incompatibility and evolution of strains are discussed.     

Molecular crosstalk in host-parasite relationships: schistosome- and leech-host interactions

The host-parasite relationship is based on subtle interplay between parasite survival strategies and host defense mechanisms. In this context, parasites often use the same or similar immune signaling molecules and/or molecular mimicry to escape host immunosurveillance. Both processes represent an adaptive strategy to ensure host immunocompatibility. This bidirectional communication between parasites and their hosts includes the renin-angiotensin, opioid and opiate systems. Here, Michel Salzet, André Capron and George Stefano review recent work on the interaction of common signaling mechanisms in schistosomes, leeches and their host.     

Stability of genetic polymorphism in host-parasite interactions

Allelic diversity is common at host loci involved in parasite recognition, such as the major histocompatibility complex in vertebrates or gene-for-gene relationships in plants, and in corresponding loci encoding antigenic molecules in parasites. Diverse factors have been proposed in models to account for genetic polymorphism in host-parasite recognition. Here, a simple but general theory of host-parasite coevolution is developed. Coevolution implies the existence of indirect frequency-dependent selection (FDS), because natural selection on the host depends on the frequency of a parasite gene, and vice versa. It is shown that polymorphism can be maintained in both organisms only if there is negative, direct FDS, such that the strength of natural selection for the host resistance allele, the parasite virulence allele or both declines with increasing frequency of that allele itself. This condition may be fulfilled if the parasite has more than one generation in the same host individual, a feature which is common to most diseases. It is argued that the general theory encompasses almost all factors previously proposed to account for polymorphism at corresponding host and parasite loci, including those controlling gene-for-gene interactions.     

Parasite immune escape: new views into host-parasite interactions

For parasites of humans and animals that rely on vectors or on sexual contact for transmission, it is particularly important that infection does not to terminate before the occurrence of the crucial event that completes its lifecycle (e.g. another mosquito bite). For chronic infection to occur, it is essential that the parasite avoids clearance by the host immune system. Much progress has been made in elucidating the immunological interactions and the molecular mechanisms involved in the process of immune evasion. Mathematical models have also been invaluable in understanding these processes, particularly in the generation of new ideas about a complex form of immune evasion known as antigenic variation whereby a major target of the host immune response is varied during the course of a single infection to avoid recognition.     

The endosymbionts of tsetse flies: manipulating host-parasite interactions

Through understanding the mechanisms by which tsetse endosymbionts potentiate trypanosome susceptibility in tsetse, it may be possible to engineer modified endosymbionts which, when introduced into tsetse, render these insects incapable of transmitting parasites. In this study we have assayed the effect of three different antibiotics on the endosymbiotic microflora of tsetse (Glossina morsitans morsitans). We showed that the broad-spectrum antibiotics, ampicillin and tetracycline, have a dramatic impact on tsetse fecundity and pupal emergence, effectively rendering these insects sterile. This results from the loss of the tsetse primary endosymbiont, Wigglesworthia glossinidia, which is eradicated by ampicillin and tetracycline treatment. Using the sugar analogue and antibiotic, streptozotocin, we demonstrated specific elimination of the tsetse secondary endosymbiont, Sodalis glossinidius, with no observed detrimental effect upon W. glossinidia. The specific eradication of S. glossinidius had a negligible effect upon the reproductive capability of tsetse but did effect a significant reduction in fly longevity. Furthermore, elimination of S. glossinidius resulted in increased refractoriness to trypanosome infection in tsetse, providing further evidence that S. glossinidius plays an important role in potentiating trypanosome susceptibility in this important disease vector. In the light of these findings, we highlight progress made towards developing recombinant Sodalis strains engineered to avoid potentiating trypanosome susceptibility in tsetse. In particular, we focus on the chitinase/N-acetyl-D-glucosamine catabolic machinery of Sodalis which has previously been implicated in causing immune inhibition in tsetse.