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| Open AccessSingle cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.
- Nicholas L. Dooley
- , Tinashe G. Chabikwa
- & Michelle J. Boyle
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Article
| Open AccessPlasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M
Malaria parasites use various molecular tactics to hijack IgM antibodies and escape the human immune system.
- Chenggong Ji
- , Hao Shen
- & Junyu Xiao
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Article
| Open AccessAntibodies to variable surface antigens induce antigenic variation in the intestinal parasite Giardia lamblia
Antigenic variation in protozoan parasites is considered a spontaneous process and antibodies to these variant antigens were cytotoxic. The clearance of the former antigen during antigenic switching is thought to occur by dilution of the original antigen. In this work, the authors provide in vitro and in vivo evidence, that low concentrations of antibodies against Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic but induce a robust stimulation of the switching process and the release of the former antigen into extracellular microvesicles. This process is mediated by antibody-induced clustering of VSPs into Lo-phase membrane microdomains through the raftophilic capability of the highly conserved transmembrane domain of the VSPs.
- Albano H. Tenaglia
- , Lucas A. Luján
- & Hugo D. Luján
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Article
| Open AccessCryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction
African Trypanosomes have developed elaborate immune evasion mechanisms. Here, the authors present the cryoelectron microscopy structures of a trypanosome surface receptor with human complement C3 and C3b, revealing several modes of complement interaction.
- Hagen Sülzen
- , Jakub Began
- & Sebastian Zoll
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Article
| Open AccessThe RRM-mediated RNA binding activity in T. brucei RAP1 is essential for VSG monoallelic expression
Monoallelic VSG expression is essential for Trypanosoma brucei survival. Competition between TbRAP1’s RNA and dsDNA binding activities ensures that TbRAP1 sustains a high level expression of the active VSG while silencing other VSGs globally.
- Amit Kumar Gaurav
- , Marjia Afrin
- & Bibo Li
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Article
| Open AccessNeutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion
The Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1) is a prime vaccine candidate for malaria. Here, the authors structurally and functionally characterise a panel of naturally acquired MSP-1 specific antibodies to identify one with potent broadly neutralising activity and better understand immune evasion mechanisms.
- Palak N. Patel
- , Thayne H. Dickey
- & Niraj H. Tolia
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Matters Arising
| Open AccessRelationship of circulating Plasmodium falciparum lifecycle stage to circulating parasitemia and total parasite biomass
- Michael F. Duffy
- , Gerry Q. Tonkin-Hill
- & Anthony T. Papenfuss
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Article
| Open AccessInvariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor
Trypanosomes evade the immune response through antigenic variation of a surface coat containing variant surface glycoproteins (VSG). They also express invariant surface glycoproteins (ISGs), which are less well understood. Here, Macleod et al. show that ISG65 of T. brucei is a receptor for complement component 3. They provide the crystal structure of T. brucei ISG65 in complex with complement C3d and show evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance in vivo.
- Olivia J. S. Macleod
- , Alexander D. Cook
- & Mark Carrington
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Article
| Open AccessThe intrinsically disordered protein TgIST from Toxoplasma gondii inhibits STAT1 signaling by blocking cofactor recruitment
Intrinsically disordered proteins (IDP) are pleotropic proteins with diverse functions. Here the authors show that an IDP, TgIST, from T. gondii blocks interferon-induced gene expression by binding to the STAT1 dimer interface and preventing the recruitment of co-transcriptional activators, CBP/p300, to STAT1 to inhibit expression of immunity genes.
- Zhou Huang
- , Hejun Liu
- & L. David Sibley
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Article
| Open AccessSelective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo
During the erythrocyte (RBC) stage of P. falciparum infection variant surface antigens (VSAs) such as PfEMP1s and RIFINs expressed on RBCs are important for infection and evasion of host innate immune system. Here, Chew et al. use a NSG mouse model, which is deficient in B, T and NK cells but retains macrophages, to show that PfEMP1 surface expression is required for in vivo adaptation as well as in vitro evasion of macrophage phagocytosis.
- Marvin Chew
- , Weijian Ye
- & Peter Preiser
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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
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Article
| Open AccessCryo-EM reveals the architecture of placental malaria VAR2CSA and provides molecular insight into chondroitin sulfate binding
In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.
- Kaituo Wang
- , Robert Dagil
- & Ali Salanti
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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
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Article
| Open AccessAmplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity
Duffy binding protein (DBP) of Plasmodium vivax is important for invasion and is a potential vaccine candidate. Here, the authors show that PvDBP gene amplification protects P vivax in vitro against invasion inhibitory human monoclonal antibodies and is associated to infection of patients with PvDBP binding inhibitory antibodies.
- Jean Popovici
- , Camille Roesch
- & Benoit Witkowski
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Article
| Open AccessVariant antigen diversity in Trypanosoma vivax is not driven by recombination
Trypanosoma rely on variant surface glycoprotein (VSG) to escape host immunity, but mechanisms generating antigenic diversity of VSG are poorly understood. Here, Silva-Pereira et al. show that T. vivax has a limited antigenic repertoire compared to T. brucei and that recombination plays little role in diversifying T. vivax VSG sequences.
- Sara Silva Pereira
- , Kayo J. G. de Almeida Castilho Neto
- & Andrew P. Jackson
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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
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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
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Article
| Open AccessVariant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation
Trypanosoma brucei evades the host immune system through replacement of a variant surface glycoprotein (VSG) coat. Here, the authors show that VSG replacement takes several days to complete, and the parasite is vulnerable to the host immune system for a short period of time during the process.
- Jason Pinger
- , Shanin Chowdhury
- & F. Nina Papavasiliou