Browsing by Subject "Host-Parasite Interactions"
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Item Open Access Behavioural ecology and infectious disease: implications for conservation of biodiversity.(Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2019-09) Herrera, James; Nunn, Charles LBehaviour underpins interactions among conspecifics and between species, with consequences for the transmission of disease-causing parasites. Because many parasites lead to declines in population size and increased risk of extinction for threatened species, understanding the link between host behaviour and disease transmission is particularly important for conservation management. Here, we consider the intersection of behaviour, ecology and parasite transmission, broadly encompassing micro- and macroparasites. We focus on behaviours that have direct impacts on transmission, as well as the behaviours that result from infection. Given the important role of parasites in host survival and reproduction, the effects of behaviour on parasitism can scale up to population-level processes, thus affecting species conservation. Understanding how conservation and infectious disease control strategies actually affect transmission potential can therefore often only be understood through a behavioural lens. We highlight how behavioural perspectives of disease ecology apply to conservation by reviewing the different ways that behavioural ecology influences parasite transmission and conservation goals. This article is part of the theme issue 'Linking behaviour to dynamics of populations and communities: application of novel approaches in behavioural ecology to conservation'.Item Open Access Cell type- and species-specific host responses to Toxoplasma gondii and its near relatives.(International journal for parasitology, 2020-05-11) Wong, Zhee S; Borrelli, Sarah L Sokol; Coyne, Carolyn C; Boyle, Jon PToxoplasma gondii is remarkably unique in its ability to successfully infect vertebrate hosts from multiple phyla and can successfully infect most cells within these organisms. The infection outcome in each of these species is determined by the complex interaction between parasite and host genotype. As techniques to quantify global changes in cell function become more readily available and precise, new data are coming to light about how (i) different host cell types respond to parasitic infection and (ii) different parasite species impact the host. Here we focus on recent studies comparing the response to intracellular parasitism by different cell types and insights into understanding host-parasite interactions from comparative studies on T. gondii and its close extant relatives.Item Open Access Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.(PLoS Pathog, 2010-02-19) O'Meara, Teresa R; Norton, Diana; Price, Michael S; Hay, Christie; Clements, Meredith F; Nichols, Connie B; Alspaugh, J AndrewCryptococcus neoformans is a prevalent human fungal pathogen that must survive within various tissues in order to establish a human infection. We have identified the C. neoformans Rim101 transcription factor, a highly conserved pH-response regulator in many fungal species. The rim101 multiply sign in circle mutant strain displays growth defects similar to other fungal species in the presence of alkaline pH, increased salt concentrations, and iron limitation. However, the rim101 multiply sign in circle strain is also characterized by a striking defect in capsule, an important virulence-associated phenotype. This capsular defect is likely due to alterations in polysaccharide attachment to the cell surface, not in polysaccharide biosynthesis. In contrast to many other C. neoformans capsule-defective strains, the rim101 multiply sign in circle mutant is hypervirulent in animal models of cryptococcosis. Whereas Rim101 activation in other fungal species occurs through the conserved Rim pathway, we demonstrate that C. neoformans Rim101 is also activated by the cAMP/PKA pathway. We report here that C. neoformans uses PKA and the Rim pathway to regulate the localization, activation, and processing of the Rim101 transcription factor. We also demonstrate specific host-relevant activating conditions for Rim101 cleavage, showing that C. neoformans has co-opted conserved signaling pathways to respond to the specific niche within the infected host. These results establish a novel mechanism for Rim101 activation and the integration of two conserved signaling cascades in response to host environmental conditions.Item Open Access Live Imaging of Host-Parasite Interactions in a Zebrafish Infection Model Reveals Cryptococcal Determinants of Virulence and Central Nervous System Invasion.(MBio, 2015-09-29) Tenor, Jennifer L; Oehlers, Stefan H; Yang, Jialu L; Tobin, David M; Perfect, John RUNLABELLED: The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus with the zebrafish innate immune system, which shares a highly conserved framework with that of mammals. Through live-imaging observations and genetic knockdown, we establish that macrophages are the primary immune cells responsible for responding to and containing acute cryptococcal infections. By interrogating survival and cryptococcal burden following infection with a panel of Cryptococcus mutants, we find that virulence factors initially identified as important in causing disease in mice are also necessary for pathogenesis in zebrafish larvae. Live imaging of the cranial blood vessels of infected larvae reveals that C. neoformans is able to penetrate the zebrafish brain following intravenous infection. By studying a C. neoformans FNX1 gene mutant, we find that blood-brain barrier invasion is dependent on a known cryptococcal invasion-promoting pathway previously identified in a murine model of central nervous system invasion. The zebrafish-C. neoformans platform provides a visually and genetically accessible vertebrate model system for cryptococcal pathogenesis with many of the advantages of small invertebrates. This model is well suited for higher-throughput screening of mutants, mechanistic dissection of cryptococcal pathogenesis in live animals, and use in the evaluation of therapeutic agents. IMPORTANCE: Cryptococcus neoformans is an important opportunistic pathogen that is estimated to be responsible for more than 600,000 deaths worldwide annually. Existing mammalian models of cryptococcal pathogenesis are costly, and the analysis of important pathogenic processes such as meningitis is laborious and remains a challenge to visualize. Conversely, although invertebrate models of cryptococcal infection allow high-throughput assays, they fail to replicate the anatomical complexity found in vertebrates and, specifically, cryptococcal stages of disease. Here we have utilized larval zebrafish as a platform that overcomes many of these limitations. We demonstrate that the pathogenesis of C. neoformans infection in zebrafish involves factors identical to those in mammalian and invertebrate infections. We then utilize the live-imaging capacity of zebrafish larvae to follow the progression of cryptococcal infection in real time and establish a relevant model of the critical central nervous system infection phase of disease in a nonmammalian model.Item Open Access Predictions of primate-parasite coextinction.(Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2021-11) Herrera, James P; Moody, James; Nunn, Charles LFuture biodiversity loss threatens the integrity of complex ecological associations, including among hosts and parasites. Almost half of primate species are threatened with extinction, and the loss of threatened hosts could negatively impact parasite associations and ecosystem functions. If endangered hosts are highly connected in host-parasite networks, then future host extinctions will also drive parasite extinctions, destabilizing ecological networks. If threatened hosts are not highly connected, however, then network structure should not be greatly affected by the loss of threatened hosts. Networks with high connectance, modularity, nestedness and robustness are more resilient to perturbations such as the loss of interactions than sparse, nonmodular and non-nested networks. We analysed the interaction network involving 213 primates and 763 parasites and removed threatened primates (114 species) to simulate the effects of extinction. Our analyses revealed that connections to 23% of primate parasites (176 species) may be lost if threatened primates go extinct. In addition, measures of network structure were affected, but in varying ways because threatened hosts have fewer parasite interactions than non-threatened hosts. These results reveal that host extinctions will perturb the host-parasite network and potentially lead to secondary extinctions of parasites. The ecological consequences of these extinctions remain unclear. This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.Item Open Access Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.(Clin Sci (Lond), 2015-11) Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme VM; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna MaeSchistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity.Item Open Access Solution NMR studies of the plant peptide hormone CEP inform function.(FEBS letters, 2013-12) Bobay, Benjamin G; DiGennaro, Peter; Scholl, Elizabeth; Imin, Nijat; Djordjevic, Michael A; Mck Bird, DavidThe C-terminally Encoded Peptide (CEP) family of regulatory peptides controls root development in vascular plants. Here, we present the first NMR structures of CEP. We show that root-knot nematode (RKN: Meloidogyne spp.) also encodes CEP, presumably to mimic plant CEP as part of their stereotypic, parasitic interaction with vascular plants. Molecular dynamics simulations of plant- and nematode-encoded CEP displaying known posttranslational modifications (PTM) provided insight into the structural effects of PTM and the conformational plasticity and rigidity of CEP. Potential mechanisms of action are discussed with respect to the structure and sampling of conformational space.Item Open Access The changing ecology of primate parasites: Insights from wild-captive comparisons.(American journal of primatology, 2019-07-02) Herrera, James P; Chakraborty, Debapriyo; Rushmore, Julie; Altizer, Sonia; Nunn, CharlesHost movements, including migrations or range expansions, are known to influence parasite communities. Transitions to captivity-a rarely studied yet widespread human-driven host movement-can also change parasite communities, in some cases leading to pathogen spillover among wildlife species, or between wildlife and human hosts. We compared parasite species richness between wild and captive populations of 22 primate species, including macro- (helminths and arthropods) and micro-parasites (viruses, protozoa, bacteria, and fungi). We predicted that captive primates would have only a subset of their native parasite community, and would possess fewer parasites with complex life cycles requiring intermediate hosts or vectors. We further predicted that captive primates would have parasites transmitted by close contact and environmentally-including those shared with humans and other animals, such as commensals and pests. We found that the composition of primate parasite communities shifted in captive populations, especially because of turnover (parasites detected in captivity but not reported in the wild), but with some evidence of nestedness (holdovers from the wild). Because of the high degree of turnover, we found no significant difference in overall parasite richness between captive and wild primates. Vector-borne parasites were less likely to be found in captivity, whereas parasites transmitted through either close or non-close contact, including through fecal-oral transmission, were more likely to be newly detected in captivity. These findings identify parasites that require monitoring in captivity and raise concerns about the introduction of novel parasites to potentially susceptible wildlife populations during reintroduction programs.