Featured
-
-
Article
| Open AccessTheileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy
Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
- Marie Villares
- , Nelly Lourenço
- & Jonathan B. Weitzman
-
Article
| Open AccessMalaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin
Blood and liver stages of malaria parasites can affect each other, but it’s not clear how this may affect live-attenuated whole parasite vaccination. Here the authors show that malaria parasite blood stage infection subdues new infection and vaccination by suppressing growth of its liver stage via host cytokines.
- Hardik Patel
- , Nana K. Minkah
- & Stefan H. I. Kappe
-
Article
| Open AccessGene expression analyses reveal differences in children’s response to malaria according to their age
Here the authors use dual RNA sequencing to characterize host and parasite gene expression from 136 Malian children with symptomatic Plasmodium falciparum infection. They find that parasitemia levels correlate with neutrophil and T cell levels and that the child’s age correlates with innate immune gene expression as well as gametocyte levels.
- Kieran Tebben
- , Salif Yirampo
- & David Serre
-
Article
| Open AccessCytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection
It is important to understand why some individuals in endemic regions acquire natural immunity against malaria while others remain susceptible. Here authors show that during episodes of Plasmodium falciparum malaria, circumsporozoite-specific cytolytic memory CD4+ T cells are clonally expanded in patients, and those with clinical immunity demonstrate reduction in the chemotactic and inhibitory receptor expression in ZEB2+ memory CD4+ T cells.
- Raquel Furtado
- , Mahinder Paul
- & Grégoire Lauvau
-
Article
| Open Access3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon intestinalis
Microsporidia are obligate intracellular parasitic fungi that can cause opportunistic infections in humans. Here, Antao et al. investigate the intracellular life cycle of human-infecting Encephalitozoon intestinalis using serial block-face scanning electron microscopy to characterize parasite organelle development and host-cell mitochondrial remodeling.
- Noelle V. Antao
- , Cherry Lam
- & Gira Bhabha
-
Article
| Open AccessIL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
-
Article
| Open AccessLocalized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease
The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.
- Zongyuan Liu
- , Rebecca Ulrich vonBargen
- & Laura-Isobel McCall
-
Article
| Open AccessGut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria
Specific gut microbiota constituents that affect the severity of malaria are unknown. Here, Mandal et al. identify specific Bacteroides species causing susceptibility to severe malaria in mice and correlate with the severity of malaria in Ugandan children.
- Rabindra K. Mandal
- , Anita Mandal
- & Nathan W. Schmidt
-
Article
| Open AccessStructure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies
The AMA1-RON2 complex is important for Plasmodium falciparum invasion and a potential vaccine target. Here the authors engineer a fusion protein of AMA1 and RON2 loop that mimics the receptor-ligand complex and show that it induces antibodies that neutralize non-vaccine type parasites.
- Sean Yanik
- , Varsha Venkatesh
- & Prakash Srinivasan
-
Article
| Open Accessγδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.
- Juan F. Quintana
- , Matthew C. Sinton
- & Annette MacLeod
-
Article
| Open AccessDevelopment of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures
Suitable in vitro models allowing to assess Plasmodium liver stage development are still limited. Here, Yang et al. show that hepatocytes derived from human hepatocyte organoids (HepOrgs) can support P. falciparum development. This allowed for the identification and validation of the importance of the host factor, scavenger receptor B1 (SRB1), in parasite development.
- Annie S. P. Yang
- , Devanjali Dutta
- & Robert W. Sauerwein
-
Article
| Open AccessPulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis
Schistosomiasis, a parasitic helminth infection, causes pulmonary symptoms during acute and chronic infection. Here, Houlder et al characterise the pulmonary immune response and demonstrate the role type 2 dendritic cells play in lung inflammation.
- E. L. Houlder
- , A. H. Costain
- & A. S. MacDonald
-
Article
| Open AccessThe Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas
This work reveals the diversity and extent of human antibody specificities in Chagas disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.
- Alejandro D. Ricci
- , Leonel Bracco
- & Fernán Agüero
-
Article
| Open AccessCryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses
Cryptosporidium parvum virus 1 is a virus harbored by the pathogenic protozoan Cryptosporidium parvum, and whose role in parasite biology and host interactions remains unclear. Here, Deng et al. demonstrate the impact this virus has on host response and infection outcome.
- Silu Deng
- , Wei He
- & Xian-Ming Chen
-
Article
| Open AccessGasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection
Here, de Sá et al. show that Gasdermin-D is transiently activated in Leishmania-infected macrophages and promotes NLRP3 inflammasome activation, but not cell death. Gasdermin-D is cleaved into a noncanonical fragment, indicating that Leishmania subverts Gasdermin-D-mediated host response to establish leishmaniasis.
- Keyla S. G. de Sá
- , Luana A. Amaral
- & Dario S. Zamboni
-
Article
| Open AccessThe Toxoplasma micropore mediates endocytosis for selective nutrient salvage from host cell compartments
Toxoplasma gondii acquires host cytosolic materials, yet the mechanism remains unknown. Wan et al. reveal the micropore as an essential organelle at the plasma membrane for endocytosis of host cytosolic proteins and biotin, and Golgi ceramide.
- Wenyan Wan
- , Hui Dong
- & Shaojun Long
-
Article
| Open AccessIL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection
Immunosuppression as a result of severe infection impairs pathogen clearance and can increase susceptibility to secondary infection. Here, the authors dissect how T cell aging and the thymic involution that occurs during this process contribute to immunosuppression and find a key role for IL-33.
- Lei Xu
- , Chuan Wei
- & Xiaojun Chen
-
Article
| Open AccessSingle cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection
Detailed insight into how the brain responds to Trypanosoma brucei infection is lacking. Here, single cell and spatial transcriptomics are integrated to characterise this response, identifying a unique crosstalk between microglia and plasma cells.
- Juan F. Quintana
- , Praveena Chandrasegaran
- & Annette MacLeod
-
Matters Arising
| Open AccessReply to: Relationship of circulating Plasmodium falciparum lifecycle stage to circulating parasitemia and total parasite biomass
- Richard Thomson-Luque
- , Lasse Votborg-Novél
- & Silvia Portugal
-
Article
| Open AccessIFN-γ stimulated murine and human neurons mount anti-parasitic defenses against the intracellular parasite Toxoplasma gondii
Toxoplasma gondii can persist in neurons in the central nervous system, presumably because neurons have limited cell-intrinsic immune responses. However, here, Chandrasekaran et al. show that IFN-gamma stimulated primary murine neurons can clear T. gondii and that IFN-gamma stimulated murine and human neurons show decreased infection rates.
- Sambamurthy Chandrasekaran
- , Joshua A. Kochanowsky
- & Anita A. Koshy
-
Article
| Open AccessHost lung microbiota promotes malaria-associated acute respiratory distress syndrome
The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections.
- Debanjan Mukherjee
- , Ângelo Ferreira Chora
- & Maria M. Mota
-
Article
| Open AccessMalaria oocysts require circumsporozoite protein to evade mosquito immunity
Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.
- Feng Zhu
- , Hong Zheng
- & Wenyue Xu
-
Article
| Open AccessDefining the early stages of intestinal colonisation by whipworms
Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.
- María A. Duque-Correa
- , David Goulding
- & Matthew Berriman
-
Article
| Open AccessRhesus macaques self-curing from a schistosome infection can display complete immunity to challenge
To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.
- Murilo Sena Amaral
- , Daisy Woellner Santos
- & Sergio Verjovski-Almeida
-
Article
| Open AccessAfucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination
Here, Larsen et al. describe differences in Fc fucosylation of P. falciparum PfEMP1-specific IgG produced in response to natural infection versus VAR2CSA-type subunit vaccination, which leads to differences in the ability to induce FcγRIIIa-dependent natural killer cell degranulation.
- Mads Delbo Larsen
- , Mary Lopez-Perez
- & Gestur Vidarsson
-
Article
| Open AccessPlasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes
To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.
- Richard Thomson-Luque
- , Lasse Votborg-Novél
- & Silvia Portugal
-
Article
| Open AccessThe apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
Repeating fever is a hallmark of malaria. Here, a large-scale forward genetic screen in malaria-causing Plasmodium falciparum identifies genes associated with parasite tolerance to host fever, including apicoplast targeted isoprenoid biosynthesis—sharing features with artemisinin resistance.
- Min Zhang
- , Chengqi Wang
- & John H. Adams
-
Article
| Open AccessA sand fly salivary protein acts as a neutrophil chemoattractant
Immune mimicry has been shown in chemokine like moieties from bacteria and viruses. Here, the authors characterise a sand fly salivary protein that induces neutrophil chemotaxis and explore its impact in a model of parasitic infection.
- Anderson B. Guimaraes-Costa
- , John P. Shannon
- & Fabiano Oliveira
-
Article
| Open AccessToxoplasma LIPIN is essential in channeling host lipid fluxes through membrane biogenesis and lipid storage
Apicomplexa generate essential lipids as combination of host fatty acids and de novo synthesized within the apicoplast. Here, the authors identify a phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as central for controlled lipid synthesis and define the host-scavenged lipidome.
- Sheena Dass
- , Serena Shunmugam
- & Cyrille Y. Botté
-
Article
| Open AccessA human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes
Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.
- Camila H. Coelho
- , Wai Kwan Tang
- & Patrick E. Duffy
-
Article
| Open AccessMechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites
Antibodies plays critical roles in the adaptive immune response to infectious agents including malaria. Here the authors defined antibody interactions with -Fcγ-receptors expressed on immune cells with sporozoites of Plasmodium falciparum, and identified specific target epitopes of antibodies.
- Gaoqian Feng
- , Bruce D. Wines
- & James G. Beeson
-
Article
| Open Access20S proteasomes secreted by the malaria parasite promote its growth
Plasmodium falciparum secretes extracellular vesicles (EVs) while growing inside red blood cells (RBCs). Here the authors show that these EVs contain assembled and functional 20S proteasome complexes that remodel the cytoskeleton of naïve human RBCs, priming the RBCs for parasite invasion.
- Elya Dekel
- , Dana Yaffe
- & Neta Regev-Rudzki
-
Article
| Open AccessStructural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum
The most advanced P. falciparum circumsporozoite protein (PfCSP)-based malaria vaccine confers partial protection. Here, Pholcharee et al. present crystal structures, binding affinities/kinetics, and in vivo protection of 8 anti-NANP antibodies to understand in vivo protection of PfCSP-targeting antibodies.
- Tossapol Pholcharee
- , David Oyen
- & Ian A. Wilson
-
Article
| Open AccessGenome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages
Using a genome-wide CRISPR screen, the authors here identify Toxoplasma genes that counteract the anti-parasitic activity of interferon gamma in murine macrophages. One of these genes, dense granule protein GRA45, is critical for the trafficking of GRA effectors and affects virulence in mice.
- Yifan Wang
- , Lamba Omar Sangaré
- & Jeroen P. J. Saeij
-
Article
| Open AccessCaspase-8 mediates inflammation and disease in rodent malaria
Inflammasome activation plays a role in malaria pathogenesis, but details aren’t well understood. Here, the authors show that caspase-8 is a central mediator of systemic inflammation in rodent malaria and that monocytes from malaria patients express active caspases-1, -4 and -8.
- Larissa M. N. Pereira
- , Patrícia A. Assis
- & Ricardo T. Gazzinelli
-
Article
| Open AccessAnalysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention
Plasmodium infection activates signaling pathways in a-nucleated erythrocytes. Here, Adderley et al. use a comprehensive antibody microarray to show that infection extensively modulates host cell signalling and that the host receptor tyrosine kinase c-MET supports Plasmodium falciparum proliferation.
- Jack D. Adderley
- , Simona John von Freyend
- & Christian Doerig
-
Article
| Open AccessGasdermin-D-dependent IL-1α release from microglia promotes protective immunity during chronic Toxoplasma gondii infection
Control over T. gondii infection in the brain involves microglial cells, but how these cells execute this control is not clear. Here the authors show that unlike IL-1β dominant macrophages, microglia are primed for gasdermin-D-dependent IL-1α production that is critical for protection against T. gondii infection.
- Samantha J. Batista
- , Katherine M. Still
- & Tajie H. Harris
-
Article
| Open AccessA second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing
Here, the authors engineer an attenuated knock-out Leishmania (LmCen−/−) vaccine that is safe in immunocompromised mice and induces an immune response and protection similar to leishmanization with wild-type Leishmania. Since LmCen−/− is antibiotic resistant marker free, it is a candidate for clinical development.
- Wen-Wei Zhang
- , Subir Karmakar
- & Hira L. Nakhasi
-
Article
| Open AccessPlasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence
Extracellular vesicles (EVs) in plasma can affect pathogenesis of parasites, but details remain unclear. Here, Toda et al. characterize plasma-derived EVs from Plasmodium vivax patients and show that PvEVs are preferentially taken up by human spleen fibroblasts, facilitating parasite cytoadherence.
- Haruka Toda
- , Miriam Diaz-Varela
- & Hernando A. del Portillo
-
Article
| Open AccessCD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes
Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8+ T cells and reducing susceptibility to autoimmune diabetes.
- Chikako Shimokawa
- , Tamotsu Kato
- & Hajime Hisaeda
-
Article
| Open AccessAn intracellular membrane protein GEP1 regulates xanthurenic acid induced gametogenesis of malaria parasites
Mosquito-derived xanthurenic acid (XA) is a trigger for gametogenesis of Plasmodium parasites. Here the authors show that the putative amino acid transporter GEP1 is required for XA-stimulated gametogenesis in Plasmodium yoelii and that it interacts with guanylyl cyclase α (GCα), a cGMP synthesizing enzyme in gametocytes.
- Yuanyuan Jiang
- , Jun Wei
- & Jing Yuan
-
Article
| Open AccessA receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies
African trypanosome infections can persist for years, but immune evasion mechanisms are not fully understood. Here, Macleod et al. identify a trypanosome receptor for mammalian factor H, a negative regulator of the alternative complement pathway, that increases parasite transmission to tsetse flies.
- Olivia J. S. Macleod
- , Jean-Mathieu Bart
- & Mark Carrington
-
Article
| Open AccessAfrican-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin
A polymorphism in human TP53 (P47S) that predominantly exists in individuals of African descent affects ferroptosis. Here, the authors show that this results in iron accumulation in macrophages leading to more productive infection by intracellular bacteria but improved anti-inflammatory response to the malarial toxin hemozoin.
- Kumar Sachin Singh
- , Julia I-Ju Leu
- & Farokh Dotiwala
-
Article
| Open AccessLung endothelial cell antigen cross-presentation to CD8+T cells drives malaria-associated lung injury
Severe malaria can be associated with respiratory complications. Here, the authors show that malaria-associated pulmonary vascular damage is a consequence of IFNγ-activated lung endothelial cells capturing, processing, and cross-presenting malaria parasite antigen to specific CD8+ T cells induced during infection.
- Carla Claser
- , Samantha Yee Teng Nguee
- & Laurent Renia
-
Article
| Open AccessA CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice
Targeted CRISPR libraries expand the use of genetic screens across experimental conditions. Here, the authors develop a method for generating and analysing small scale custom CRISPR libraries and use it in the human and livestock pathogen Toxoplasma gondii to identify virulence factors in mice.
- Joanna Young
- , Caia Dominicus
- & Moritz Treeck
-
Article
| Open AccessThe major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function
In the study, the authors identify a protein excreted by the parasite Trichuris muris, p43, which can modulate IL-13 function, a key cytokine involved in host protection. These data suggest that p43 may be a novel therapeutic target for both whipworm infections and IL13 mediated pathologies.
- Allison J. Bancroft
- , Colin W. Levy
- & Richard K. Grencis
-
Article
| Open AccessMolecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice
Toxoplasma gondii virulence in wild-derived mice is restricted by Immunity-Related GTPases (IRG). Here, the authors show specific binding of the IRG tandem protein Irgb2-b1 with the virulence effector ROP5, and provide insights into how different ROP5 isoforms and IRG alleles shape virulence among T. gondii strains.
- Mateo Murillo-León
- , Urs B. Müller
- & Tobias Steinfeldt
-
Article
| Open AccessDual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.
- Gregory M. LaMonte
- , Pamela Orjuela-Sanchez
- & Elizabeth A. Winzeler
-
Article
| Open AccessEfficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins
Giardia lamblia express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host´s intestine. Here the authors show that stability and immunomodulatory properties of VSPs can be exploited to both protect and adjuvant vaccine antigens for oral administration.
- Marianela C. Serradell
- , Lucía L. Rupil
- & Hugo D. Luján