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| Open AccessFactor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification
Streptococcus pneumoniae evades the action of the complement system by expressing an immuno-protective polysaccharide capsule as well as Factor H-binding proteins. Here, Pathak et al. show that these two defence mechanisms are functionally and spatially coordinated on the bacterial cell surface.
- Anuj Pathak
- , Jan Bergstrand
- & Birgitta Henriques-Normark
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| Open AccessZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response
cGAS is an important mediator of antiviral immune responses, but the regulation of its activity is unknown. Here, the authors identify a zinc finger protein, ZCCHC3, that enhances the binding of cGAS to dsDNA and is important for its activation following viral infection.
- Huan Lian
- , Jin Wei
- & Hong-Bing Shu
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| Open AccessIron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.
- Angeliki M. Andrianaki
- , Irene Kyrmizi
- & Georgios Chamilos
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| Open AccessPI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner
Antibody mediated immune responses to Streptococcus pneumoniae are crucial for the immune response to infection. Here the authors show hyper-activation of PI3Kδ promotes development of a subset of B cells that exacerbate infection in an antibody-independent manner and can be reversed by therapeutic targeting in vivo.
- Anne-Katrien Stark
- , Anita Chandra
- & Klaus Okkenhaug
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| Open AccessCross-reactive Dengue virus-specific CD8+ T cells protect against Zika virus during pregnancy
Heterologous immunity can confer protection between related viruses. Here the authors show that prior exposure to Dengue virus can protect against subsequent infection with Zika virus in the context of pregnancy, and crucially can prevent demise of the fetus in murine models of infection.
- Jose Angel Regla-Nava
- , Annie Elong Ngono
- & Sujan Shresta
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| Open AccessA TRAF3-NIK module differentially regulates DNA vs RNA pathways in innate immune signaling
The innate immunity system detects viral pathogens by sensing viral DNA or RNA via distinct pathways, but whether these pathways cross-regulate is unclear. Here the authors show that TRAF3, a known regulator of the RNA-sensing pathway, modulates an NF-κB activator NIK to control DNA-sensing by the adaptor STING in immune cells.
- Kislay Parvatiyar
- , Jose Pindado
- & Genhong Cheng
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| Open AccessUBXN3B positively regulates STING-mediated antiviral immune responses
The UBXN proteins are likely involved in a diverse range of biological processes, but their physiological functions remain largely unknown. Here the authors show that UBXN3B positively regulates STING-mediated immune responses in the context of viral infections.
- Long Yang
- , Leilei Wang
- & Penghua Wang
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| Open AccessMultiple communication mechanisms between sensor kinases are crucial for virulence in Pseudomonas aeruginosa
Bacteria respond to stresses using two-component systems consisting of sensor kinases (SKs) and response regulators. Here, Francis et al. reveal three specific interaction mechanisms between a pair of SKs that are important for regulation of virulence in the pathogen Pseudomonas aeruginosa.
- Vanessa I. Francis
- , Elaine M. Waters
- & Steven L. Porter
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| Open AccessThe hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages
The effects of iron on vacuole-resident Salmonella in macrophages are unclear. Here the authors show that the bacteria are not subject to nutritional inhibition by iron deprivation, but that iron depletion in the vacuole, via the hepcidin-ferroportin axis, inhibits the bactericidal effect of oxidative burst.
- Daejin Lim
- , Kwang Soo Kim
- & Hyon E. Choy
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| Open AccessCanonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis
Trypanosoma cruzi infection causes Chagas disease, but mechanisms underlying pathogenesis are unclear. Here, Silva et al. show that canonical PI3Kγ signaling in myeloid cells restricts T. cruzi infection in mice and that high PIK3CG expression correlates with low parasite levels in human Chagas’ hearts.
- Maria C. Silva
- , Marcela Davoli-Ferreira
- & Thiago M. Cunha
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| Open AccessA community approach to mortality prediction in sepsis via gene expression analysis
Sepsis is characterized by deregulated host response to infection. Efficient therapies are still needed but a limitation for sepsis treatment is the heterogeneity in patients. Here Sweeney et al. generate prognostic models based on gene expression to improve risk stratification classification and prediction for 30-day mortality of patients.
- Timothy E. Sweeney
- , Thanneer M. Perumal
- & Raymond J. Langley
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| Open AccessDevelopment of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone
Given the recent Zika virus (ZIKV) epidemic, development of an effective vaccine is of high importance. Here, the authors use a licensed live-attenuated flavivirus vaccine backbone to develop a ZIKV vaccine and determine immunogenicity, safety and protection profiles in different animal models.
- Xiao-Feng Li
- , Hao-Long Dong
- & Cheng-Feng Qin
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| Open AccessMAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A
Most MAIT cell response to infection studies are of mice. Here the authors characterize MAIT cell population responses to Salmonella Paratyphi A infection of 25 human volunteers using TCR clonotype analysis and mass cytometry of pre-infection matched to post-infection samples.
- Lauren J. Howson
- , Giorgio Napolitani
- & Vincenzo Cerundolo
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| Open AccessHuman caspase-4 detects tetra-acylated LPS and cytosolic Francisella and functions differently from murine caspase-11
Lipid A from some bacteria is sensed differently by humans and mice for the activation of the inflammasomes and inflammatory responses, but the mechanisms are not clear. Here, the authors show that murine caspase-11 and human caspase-4/5 contribute to this differential response via their distinct recognition of under-acylated lipid A.
- Brice Lagrange
- , Sacha Benaoudia
- & Thomas Henry
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| Open AccessStaphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314
Bacterial infection can cause pain but the underlying mechanism is unclear. This study shows pain induced in mice by methicillin-resistant Staphylococcus aureus infection is mediated by bacterial pore-forming toxins, and a sodium channel blocker QX-314 can alleviate infection-associated pain.
- Kimbria J. Blake
- , Pankaj Baral
- & Isaac M. Chiu
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| Open AccessCLEC5A is a critical receptor in innate immunity against Listeria infection
The lectin receptor CLEC5A is a pattern recognition receptor that has been shown to detect dengue and Japanese encephalitis virus. Here the authors show that CLEC5A is needed for optimal ROS production, NET formation and other immune responses to Listeria monocytogenes in mice.
- Szu-Ting Chen
- , Fei-Ju Li
- & Shie-Liang Hsieh
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| Open AccessTwo forms of death in ageing Caenorhabditis elegans
Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.
- Yuan Zhao
- , Ann F. Gilliat
- & David Gems
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| Open AccessIL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population
Patients who survive sepsis are at increased risk of infection owing to long-term immunosuppression that is associated with an increase in Treg cell numbers. Here the authors show expansion of the Treg cell population in sepsis mice is driven by IL-33-induced ILC2 activation of IL-10 production by macrophages.
- Daniele C. Nascimento
- , Paulo H. Melo
- & Jose C. Alves-Filho
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| Open AccessRegulation of phagocyte triglyceride by a STAT-ATG2 pathway controls mycobacterial infection
Cytokines and their associated pathways can affect survival ofMycobacterium tuberculosis in macrophages, representing potential targets for host-directed therapies. Here, Péan et al. show that cytokine-STAT signalling promotes mycobacterial survival within macrophages by deregulating lipid droplet homeostasis.
- Claire B. Péan
- , Mark Schiebler
- & Marc S. Dionne
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| Open AccessHigh-throughput automated microfluidic sample preparation for accurate microbial genomics
Shotgun DNA sequencing experiments for microbial genomic analysis are often impractical due to minimum sample input requirements. Here the authors develop a microfluidic sample preparation platform that reduces sample input requirements 100-fold and enables high throughput sequencing from low numbers of cells.
- Soohong Kim
- , Joachim De Jonghe
- & Paul C. Blainey
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| Open AccesstRNA-mediated codon-biased translation in mycobacterial hypoxic persistence
Mycobacteria can adapt to the stress of human infection by entering a dormant state. Here the authors show that hypoxia-induced dormancy in M. bovisBCG involves the reprogramming of tRNA wobble modifications and copy numbers, coupled with biased use of synonymous codons in survival genes.
- Yok Hian Chionh
- , Megan McBee
- & Peter C. Dedon
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| Open AccessOxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes
Carriers of haemoglobinopathies are protected from severe malaria, likely due to reduced surface expression of virulence factors. Here, Cyrklaff et al. show that, similar to haemoglobinopathies, a transient oxidative insult affects actin reorganization and mitigates the development of cerebral malaria in mice.
- Marek Cyrklaff
- , Sirikamol Srismith
- & Michael Lanzer
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| Open AccessGrowth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death
Inflammatory caspases restrict microbial growth by inducing cytokine production and pyroptosis, but other caspase-induced mechanisms are thought to contribute. Here the authors use time-lapse microscopy of single cells to show that caspase1/11 has anti-Salmonella functions that occur in advance of cell death induction.
- Teresa L. M. Thurston
- , Sophie A. Matthews
- & David W. Holden
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| Open AccessInhibition of ROS and upregulation of inflammatory cytokines by FoxO3a promotes survival against Salmonella typhimurium
FoxO3a signalling has limited influence over acute bacterial infection. Here the authors show that FoxO3a promotes survival of mice in response to chronic Salmonellatyphimurium infection by restraining oxidative stress and ERK signalling.
- Julie Joseph
- , Emmanuelle S. Ametepe
- & Subash Sad
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| Open AccessFat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation
Fat-associated lymphoid clusters (FALC) in the serous cavities house rapid IgM-producing B1 cells, but how the clusters are activated to respond to infection is unclear. Here the authors show that in response to lung inflammation or pleural nematode infection adipose stromal cell-derived IL-33 activates ILC2s to produce IL-5, thus driving the B1 response in the FALCs.
- Lucy H. Jackson-Jones
- , Sheelagh M. Duncan
- & Cécile Bénézech
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| Open AccessIdentification of Siglec-1 null individuals infected with HIV-1
Binding of virus, HIV-1, to cellular protein Siglec-1 is important for infection of immune cells. Here the authors show that a natural mutation leading to production of truncated Siglec-1 reduces HIV binding and infectivity transfer in vitro, but does not substantially affect infection or AIDS outcome in patients.
- Javier Martinez-Picado
- , Paul J. McLaren
- & Amalio Telenti
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Infection-induced type I interferons activate CD11b on B-1 cells for subsequent lymph node accumulation
Tissue-resident B-1 cells express CD11b, unlike their lymphoid organ-residing counterparts. Here the authors show that influenza-induced type I interferons activate CD11b on B-1 cells, facilitating entry to mediastinal lymph nodes, where they provide the first line of antibody-mediated host defense.
- Elizabeth E. Waffarn
- , Christine J. Hastey
- & Nicole Baumgarth
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| Open AccessTranscriptional specialization of human dendritic cell subsets in response to microbial vaccines
The effects of vaccines on human dendritic cells (DCs) are incompletely understood. Here the authors build a transcriptional modular network based on in vitroinfection of human DCs and apply it for the characterization of the DC response to 13 different vaccines.
- Romain Banchereau
- , Nicole Baldwin
- & Virginia Pascual
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NK1.1+ CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response
Antigen-specific CD8 T cells expand during an infection and then contract, eliminating all but a small population of memory cells. Here the authors show that NK1.1+CD8 T cells have innate-like features at the memory stage, undergo delayed contraction and provide protection against early re-infection.
- Anne L. Ruiz
- , Saidi M’Homa Soudja
- & Julien C. Marie
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IKKα negatively regulates ASC-dependent inflammasome activation
The molecular mechanisms mediating inflammasome activation are not fully elucidated. Here the authors show that the kinase IKKα interacts in the nucleus and perinuclear area with the adaptor molecule ASC, negatively regulating inflammasome activation.
- Bradley N. Martin
- , Chenhui Wang
- & Xiaoxia Li
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Fucose-specific DC-SIGN signalling directs T helper cell type-2 responses via IKKε- and CYLD-dependent Bcl3 activation
C-type lectin receptor DC-SIGN, expressed on dendritic cells, shapes cytokine production in response to pathogens. Here, the authors show how recognition of fucose-expressing pathogens, Schistosoma mansoni and Helicobacter pylori, by this receptor directs T helper cell type-2 responses via activation of the NF-κB family member Bcl3.
- Sonja I. Gringhuis
- , Tanja M. Kaptein
- & Teunis B. H. Geijtenbeek
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An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing
Toll-like receptor 9 detects microbial DNA, and is activated by cleavage in the endolysosome. Onji et al. discover that following cleavage, the two parts of the protein remain associated, and this interaction is required for DNA sensing.
- Masahiro Onji
- , Atsuo Kanno
- & Kensuke Miyake
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| Open AccessStretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope
Bacteria express adhesive proteins on their surface that recognize fibronectin. Using a mechanical stretch assay and steered molecular dynamics, Chabriaet al. demonstrate that the binding of a bacterial adhesin to fibronectin is mechanoregulated, suggesting that bacteria can sense tissue fibre stretching.
- Mamta Chabria
- , Samuel Hertig
- & Viola Vogel