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| Open AccessThe anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand
Schistosomiasis is caused by infection with the flatworm Schistosoma, and praziquantel is the drug of choice for its treatment. Here, Chan and colleagues identify praziquantel as a ligand for the human serotoninergic 5-HT2B G-protein-coupled receptor, and reveal a function for praziquantel as a regulator of vascular tone in treated hosts.
- John D. Chan
- , Pauline M. Cupit
- & Jonathan S. Marchant
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| Open AccessA structurally distinct TGF-β mimic from an intestinal helminth parasite potently induces regulatory T cells
Heligmosomoides polygyrus can activate mammalian TGF-β signalling pathways, but how it does so is not known. Here the authors identify and isolate a H. polygyrus TFG-β mimic that can bind both mammalian TGF-β receptor subunits, activate Smad signalling and generate inducible regulatory T cells.
- Chris J. C. Johnston
- , Danielle J. Smyth
- & Rick M. Maizels
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| Open AccessExamining the human infectious reservoir for Plasmodium falciparum malaria in areas of differing transmission intensity
Heterogeneity in the transmission potential of individual hosts is an important feature of malaria. Here, the authors perform a multi-regional study of the human infectious reservoir in malaria-endemic regions of Burkina Faso and Kenya.
- Bronner P. Gonçalves
- , Melissa C. Kapulu
- & Teun Bousema
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| Open AccessInteractions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis
The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor.
- Lalit Kumar Dubey
- , Praneeth Karempudi
- & Nicola L. Harris
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| Open AccessInnate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection
Scavenger receptors can function as pattern recognition receptors to sense infection. Here the authors show that, in response to worm and bacterial infection, scavenger receptor class A prevents nuclear localization of IRF5 and thereby drives M2 polarization and associated type 2 immune responses.
- Zhipeng Xu
- , Lei Xu
- & Chuan Su
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Article
| Open AccessSkin parasite landscape determines host infectiousness in visceral leishmaniasis
Parasitemia has been considered the main determinant of visceral leishmaniasis transmission. By combining imaging, qPCR and experimental xenodiagnoses with mathematical models, Doehl et al. argue that the patchy landscape of parasites in the skin is necessary to explain infectiousness.
- Johannes S. P. Doehl
- , Zoe Bright
- & Paul M. Kaye
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| Open AccessMyosin-dependent cell-cell communication controls synchronicity of division in acute and chronic stages of Toxoplasma gondii
The mechanism by whichToxoplasma gondiiachieves synchronized cell division is incompletely understood. Here, the authors identify an intravacuolar cell-cell communication that ensures synchronized division and depends on myosin I.
- Karine Frénal
- , Damien Jacot
- & Dominique Soldati-Favre
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| Open AccessArylmethylamino steroids as antiparasitic agents
Steroid units can facilitate membrane permeation and bioavailability in drugs. Here, using a medicinal chemistry program, Krieget al. identify an arylmethylamino steroid that kills Plasmodium parasites, likely through a chelate-based quinone methide mechanism, and has activity against Schistosoma mansoni.
- Reimar Krieg
- , Esther Jortzik
- & Katja Becker
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Article
| Open AccessmTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
mTORC1 and mTORC2 are alternatively required for differentiation of T cells into Th1/Th17 or Th2 cells. Here the authors show mTORC2 signalling is also needed for IL-4-induced M2 activation with functional evidence provided by aN. brasiliensisinfection model and cold challenge to model adaptive thermogenesis.
- R. W. Hallowell
- , S. L. Collins
- & M. R. Horton
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| Open AccessUnconventional endosome-like compartment and retromer complex in Toxoplasma gondii govern parasite integrity and host infection
The retromer complex is a multi-protein component of the endosomal protein sorting machinery. Here, Sangaré et al. identify unique features in the retromer complex of the parasite Toxoplasma gondii, and show that it is crucial for the biogenesis of secretory organelles in this pathogen.
- Lamba Omar Sangaré
- , Tchilabalo Dilezitoko Alayi
- & Stanislas Tomavo
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Article
| Open AccessAncient human sialic acid variant restricts an emerging zoonotic malaria parasite
Plasmodium knowlesi infects macaques and can cause malaria in humans. Here, Dankwa et al. show that the absence of a sialic-acid component on the surface of macaque red blood cells (RBCs) limits infection of human RBCs with P. knowlesi, but the parasite can adapt to invade human RBCs by using alternative pathways.
- Selasi Dankwa
- , Caeul Lim
- & Manoj T. Duraisingh
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| Open AccessDefining the relationship between infection prevalence and clinical incidence of Plasmodium falciparum malaria
Mathematical models are used to predict malaria burden to inform disease control efforts. Here, Cameron et al. use Bayesian statistics to calibrate previous models against a data set of age-structured prevalence and incidence, generating stratified forecasts of the prevalence–incidence relationship.
- Ewan Cameron
- , Katherine E. Battle
- & Peter W. Gething
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| Open AccessPlasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice
Mice engrafted with human cells are useful models for research on human malaria parasites. Here the authors show that the complete life cycle of Plasmodium falciparum and the liver stages of Plasmodium ovalecan be studied in mice doubly engrafted with human primary hepatocytes and red blood cells.
- Valérie Soulard
- , Henriette Bosson-Vanga
- & Dominique Mazier
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| Open AccessCaenorhabditis elegans is a useful model for anthelmintic discovery
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegansto identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.
- Andrew R. Burns
- , Genna M. Luciani
- & Peter J. Roy
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| Open AccessLucilia cuprina genome unlocks parasitic fly biology to underpin future interventions
Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.
- Clare A. Anstead
- , Pasi K. Korhonen
- & Robin B. Gasser
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| Open AccessA mosquito lipoxin/lipocalin complex mediates innate immune priming in Anopheles gambiae
A soluble factor induced by Plasmodiuminfection promotes hemocyte differentiation and increases mosquitoe resistance to subsequent infections. Here the authors show that this factor consists of a Lipocalin/Lipoxin A4 complex, and that insects can metabolize arachidonic acid to produce lipoxins.
- Jose Luis Ramirez
- , Giselle de Almeida Oliveira
- & Carolina Barillas-Mury
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| Open AccessContrasting host–pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes
Microsporidia are intracellular parasitic fungi that infect diverse animal hosts including humans. Here, Desjardins et al.present genomic and transcriptomic data for two microsporidia that infect disease-transmitting mosquitoes, highlighting differences in potential host interplay mechanisms.
- Christopher A. Desjardins
- , Neil D. Sanscrainte
- & Christina A Cuomo
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ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms
The life cycle of parasitic hookworms includes a developmental stage in the lungs, before reaching the gut where they mature into adults. Here Bouchery et al. show that Group 2 innate lymphoid cells (ILC2s) cooperate with CD4+T cells to inhibit the development of a model hookworm in the lungs of mice.
- Tiffany Bouchery
- , Ryan Kyle
- & Graham Le Gros
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| Open AccessGenetic blueprint of the zoonotic pathogen Toxocara canis
Toxocara canis is a zoonotic parasite of major worldwide socioeconomic importance. Here, the authors sequence the genome and transcriptome of T. canis, and highlight potential mechanisms involved in development and host–parasite interactions that could support the pursuit of new drug interventions.
- Xing-Quan Zhu
- , Pasi K. Korhonen
- & Robin B. Gasser
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| Open AccessExosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity
Mammalian cell-derived exosomes can carry RNA and proteins from cell to cell, but this mode of transport has not been shown in nematodes. Here the authors show that a gastrointestinal parasite secretes exosomes that transfer microRNAs to mammalian cells and regulate innate immunity.
- Amy H. Buck
- , Gillian Coakley
- & Rick M. Maizels
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| Open AccessOmega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo
Schistosomiasis, a neglected tropical disease, is caused by flatworms such as Schistosoma mansoni. Here, Hagen et al. describe a lentivirus-based transduction system to deliver microRNA-adapted small hairpin RNAs into S. mansonito inhibit transcription of selected genes implicated in the disease process.
- Jana Hagen
- , Neil D. Young
- & Bernd H. Kalinna
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Host–parasite network structure is associated with community-level immunogenetic diversity
Genes of the major histocompatibility complex (MHC) are crucial for immune response, yet it is unclear what shapes their diversity at a community level. Here, the authors show that indirect effects among rodent hosts and their helminth parasites can play a crucial role in shaping host MHC diversity.
- Shai Pilosof
- , Miguel A. Fortuna
- & Jordi Bascompte
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The parasite Entamoeba histolytica exploits the activities of human matrix metalloproteinases to invade colonic tissue
The protozoan parasite Entamoeba histolyticainvades the colon and remodels the extracellular matrix, and the parasite-derived proteinase A5 (CP-A5) is known to be involved. Here, the authors show that CP-A5 activates metalloproteinases in the host, changing colon architecture and aiding tissue invasion.
- Roman Thibeaux
- , Patrick Avé
- & Elisabeth Labruyère
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Plasticity and redundancy among AMA–RON pairs ensure host cell entry of Toxoplasma parasites
Apicomplexan parasites such as Toxoplasma gondii and Plasmodium form a tight, moving junction with host cells before invading them. Here the authors show that the proteins AMA1 and RON2 of T. gondiicooperate during junction formation and identify additional proteins that have a role in this process.
- Mauld H. Lamarque
- , Magali Roques
- & Maryse Lebrun
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Perpetual expression of PAMPs necessary for optimal immune control and clearance of a persistent pathogen
Pathogen-associated molecular patterns are involved in the initiation of anti-pathogen immunity but their importance for sustaining this response is not established. Here, the authors show that persistent presence of pathogen-associated molecular patterns is required to maintain robust immune responses to pathogens.
- Samarchith P. Kurup
- & Rick L. Tarleton
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| Open AccessApical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion
Plasmodium and Toxoplasma apical membrane antigen 1 (AMA1) is believed to be actively involved in host cell invasion by these parasites. Bargieri et al. now demonstrate that although AMA1 facilitates adhesion, invasion can proceed in the absence of the protein.
- Daniel Y. Bargieri
- , Nicole Andenmatten
- & Robert Ménard
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| Open AccessRapid and adaptive evolution of MHC genes under parasite selection in experimental vertebrate populations
In vertebrates parasite-mediated selection is thought to maintain polymorphism in MHC genes where specific resistance MHC alleles increase under emerging selection. Here, experimental evidence is shown from six stickleback fish populations that varying parasite selection helps maintain MHC polymorphism.
- Christophe Eizaguirre
- , Tobias L. Lenz
- & Manfred Milinski