Systems analysis of host-parasite interactions.

Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies

Influence of cold on host-parasite interactions.

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The influence of biological rhythms on host–parasite interactions

Biological rhythms, from circadian control of cellular processes to annual cycles in life history, are a main structural element of biology. Biological rhythms are considered adaptive because they enable organisms to partition activities to cope with, and take advantage of, predictable fluctuations in environmental conditions. A flourishing area of immunology is uncovering rhythms in the immune system of animals, including humans. Given the temporal structure of immunity, and rhythms in parasite activity and disease incidence, we propose that the intersection of chronobiology, disease ecology, and evolutionary biology holds the key to understanding host–parasite interactions. Here, we review host–parasite interactions while explicitly considering biological rhythms, and propose that rhythms: influence within-host infection dynamics and transmission between hosts, might account for diel and annual periodicity in host–parasite systems, and can lead to a host–parasite arms race in the temporal domain

Calcium Builds Strong Host-Parasite Interactions

Apicomplexan parasite invasion of host cells is a multistep process, requiring coordinated events. In this issue of Cell Host & Microbe, Paul et al. (2015) and Philip and Waters (2015) leverage experimental genetics to show that the calcium-regulated protein phosphatase, calcinuerin, regulates invasion in multiple parasite species

Host-parasite interactions in Galapagos seabirds

Parasites exhibit a wide range of life history strategies that contribute to different dispersal abilities, host specialization, transmission modes, life-cycle complexity and population structure. Understanding dispersal rates in hosts and parasites is instrumental in defining the scale at which coevolution may be occurring. In order to better understand how and when parasites move between different hosts, I studied a seabird – Hippoboscid fly ectoparasite (and vector) – Haemosporidian parasite system in the Galapagos Islands. I began by describing the Haemosporidian parasites of Galapagos seabirds, discovering a Plasmodium species parasite in Galapagos Penguins (Sphensicus mendiculus), and a new clade of Hippoboscid-vectored parasites belonging to the subgenus Haemoproteus infecting frigatebirds (Fregata spp.) and gulls (Creagrus furcatus). Despite strong genetic differentiation between Galapagos frigatebirds and their conspecifics, we found no genetic differentiation in their Haemoproteus parasite. This led me hypothesize that the movement of the Haemosporidian parasite was facilitated by the movement of the Hippoboscid fly vector. In order to answer this question, I used a comparative population genetic study of Galapagos Great Frigatebirds (F. minor), Nazca Boobies (Sula granti), and their respective Hippoboscid fly parasites (Olfersia spinifera, O. aenescens) to better understand movement of flies at the geographic scale of the archipelago. I found high levels of gene flow in both fly species, despite marked differences in the degree of population genetic structure of their bird hosts. This suggests that host movement, (and therefore parasite movement), is not necessarily associated with true host dispersal, where dispersal is followed by successful reproduction. Finally, I examined local (within island colony) transmission in the Great Frigatebird, Haemoproteus iwa, Olfersia spinifera system. I inferred movement, or host-switching, by analyzing host (frigatebird) microsatellite markers run on DNA amplified from the fly. Using the most variable microsatellite markers, we are able to identify host genotypes in bloodmeals that do not match the host from which the fly was collected. Flies that were not infected with H. iwa were more likely to have a bloodmeal that did not match the genotype of their host and female birds were the more likely recipients of host-switching flies

Host-Parasite Interactions Within Food Webs

Parasitism is one of the most common life history strategies employed in nature, yet the effects of parasites are often thought to be minimal, and the vast majority of studies fail to consider parasites and their effects on host organisms. This is likely a problem, as the magnitude of parasite-mediated effects on their hosts can be quite large. Additionally, the effects of parasites are known to extend beyond the host to affect other species interactions. I used a series of approaches to gain a more integral understanding of host-parasite interactions by studying (1) the effects of parasites on biotic interactions that hosts engage in, (2) how biotic interactions such as predation and competition can affect host immune defense, and (3) how abiotic and biotic factors within the local environment affecting the host can further mediate parasitism dynamics. Specifically, in Chapter 1 I conducted a phylogenetically informed meta-analysis of the effects of parasites on species interactions (i.e., predation, competition, mutualism, and reproduction). I found that despite a strong overall negative effect on species interactions, the effects of parasites surprisingly ranged from being strongly beneficial to strongly deleterious on host species interactions. In Chapter 2 I used larval damselflies and their dominant fish predator to test how cascading effects of predators on host competitive interactions and resource acquisition affected a critical component of damselfly immune function, the phenoloxidase (PO) cascade. I found that neither direct density-mediated effects, indirect, trait-mediated effects, nor combined effects of predators via natural selection affected total PO activity. Instead, PO levels increased with resource availability, implying resource limitation. Finally, in Chapter 3 I used two field experiments and a detailed observational study to investigate how host, abiotic, and biotic factors within the local environment affected the relationships between damselfly (Enallagma spp.) hosts and their water mite (Arrenururs spp.) ectoparasites. I found that parasitism was species-specific and did not vary with host density or host condition (i.e., immune function). Instead, parasitism was largely predicted by abiotic factors (i.e., pH). Collectively, my results indicate that parasites are key players in the complex web of species interactions that compose food webs. Furthermore, host-parasite interactions are mediated by many of the same ecological factors as other species interactions, which has implications for parasitism dynamics within ecological communities. Future studies of food webs must incorporate parasites into their experimental and theoretical designs, and future studies of host-parasite interactions must expand beyond the focal relationship and consider the ecology of both the host and parasite

Host-parasite interactions of larval cestode infections

This work is a study of the ability of three metacestode species: Taenia crassiceps, Taenia taeniaeformis and secondary infections of Echinococcus granulosus to interfere with the host's immune response.Both mice and gerbils infected with secondary hydatidosis were found to have a low antibody response to a somatic preparation of Eh granulosus as detected by ELISA throughout infection despite, in some cases, the presence of a large cyst burden. The possibility that this was the result of suppression of the host's immune response was investigated by studying the response of mice infected with secondary hydatidosis and also the murine models of metacestode disease T. crassiceps and T. taeniaeformis, to a subsequent infection of the haemoprotozoan, Babesia microti. The host susceptibility to the secondary infection was assessed by the percentage number of red blood cells that were infected and the serological response to 13. microti, as detected by IFAT, throughout the infection. All three metacestode species were found to have enhanced parasitaemias and consistently lower antibody titres to B. microti than the Babesia only infected controls. The rate of decline in the parasitaemia from peak was markedly slower in the concurrently infected mice indicating that the suppression not only affected the development of the infection but also the speed of the host's ability to resolve it.Metacestode extracts prepared from the surface of the parasites have been shown to cause a degree of cytotoxicity when added to a lymphosarcoma cell line culture. These same extracts and excretory secretory products of the metacestodes also depressed the normal Con A blastic response of MLNC from both naive and infected donor mice, to a significant extent. When living hydatid cysts are placed in culture with MLNC the normal Con A blastic response is again depressed. The MLNC from infected donors showed a greater depression of the Con A response than the cells from naive donors. The longer the period of culture of the MLNC with the hydatid cyst, the greater the depression of the Con A response. The reverse situation was found when T. crassiceps metacestodes were cultured with MLNC, as a greater depression of the Con A blastic response was found when the cells were exposed to the metacestodes for a shorter period of culture. This result was difficult to account for and required repetition.Various mechanisms were proposed for the generalised suppression induced by metacestode disease. These include antigeniccompetition, direct cytotoxic effects of parasite-derived factors and interference by parasite secreted substances with lymphocyte function. It is likely that several mechanisms account for the observed immuno¬ suppressive effects of metacestode infections on the host but without further investigation of the nature of the suppressive factors, and the target cells they act on, no defined interaction between host and parasite can be postulated