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| Open AccessNLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease
The inflammasome is normally activated by pathogens to induce tissue inflammation. Here the authors show that, in mouse experimental colitis models, Nlrp1 inflammasome sensor activates IL-18 to reduce beneficial colonic Clostridiales species, thereby decreasing microbial butyrate and its protective effects on colitis.
- Hazel Tye
- , Chien-Hsiung Yu
- & Seth L. Masters
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Article
| 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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Article
| Open AccessSensing of cytosolic LPS through caspy2 pyrin domain mediates noncanonical inflammasome activation in zebrafish
In humans, caspase-5 is an LPS sensor that can induce gasdermin D cleavage and pyroptosis. Here, the authors show that zebrafish caspy2 is a functional homolog as it also senses cytosolic LPS to activate the noncanonical inflammasome and to protect against bacterial infection, but it does so via pyrin death domain interactions.
- Dahai Yang
- , Xin Zheng
- & Qin Liu
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Article
| Open AccessDownregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop
The authors show that NDR1 promotion of STAT1 translation is an important event for IFN-dependent antiviral immune response. These data suggest that NDR1 has an important role in controlling viral infections.
- Zhiyong Liu
- , Qiang Qin
- & Xiaojian Wang
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Article
| Open AccessCorticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations
Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia. Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ.
- Aran Singanayagam
- , Nicholas Glanville
- & Sebastian L. Johnston
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Article
| Open AccessX-ray structure of a carpet-like antimicrobial defensin–phospholipid membrane disruption complex
Defensins are cationic antimicrobial peptides that permeabilize membranes of pathogens presumably via the assembly of defensin–lipid oligomers. Here authors provide evidence for this by solving the crystal structure of a plant defensin in an oligomeric state with phospholipids.
- Michael Järvå
- , Fung T. Lay
- & Marc Kvansakul
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Article
| Open AccessIdentification of the fungal ligand triggering cytotoxic PRR-mediated NK cell killing of Cryptococcus and Candida
Natural killer (NK) cells has been show to mediate fungi killing via the activating receptor NKp30, but the fungal target for NKp30 is still unclear. Here the authors show, using atomic force microscopy and live cell imaging, that β-1,3-glucan is expressed by Cryptococcus neoformans and Candida albicans and responsible for NKp30-mediated NK killing.
- Shu Shun Li
- , Henry Ogbomo
- & Christopher H. Mody
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Article
| Open AccessCrystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp
Factor H binding protein (fHbp) is a meningococcal virulence factor and a component of vaccines against serogroup B Neisseria meningitidis. Here, the authors characterize the vaccine-elicited human antibody Fab 1A12 and present both the free and the fHbp-bound Fab 1A12 crystal structures.
- Jacinto López-Sagaseta
- , Peter T. Beernink
- & Matthew J. Bottomley
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Article
| 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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Article
| 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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Article
| Open AccessHepatitis B virus persistence in mice reveals IL-21 and IL-33 as regulators of viral clearance
Hepatitis B virus (HBV) establishes chronic infection in only some patients, but the mechanisms underlying clearance failure in these patients are not fully understood. Here, the authors identify and characterize an HBV strain that can persist in mice and show that IL-21 and IL-33 responses contribute to clearance.
- Zhongliang Shen
- , Huijuan Yang
- & Jing Liu
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Article
| Open AccessGalectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects
The protein Galectin-3 modulates host immunity and plays roles during infections. Here, Almeida et al. show that this protein contributes to host defence against infection with the fungal pathogen Cryptococcus neoformans by inhibiting fungal growth and inducing lysis of fungal extracellular vesicles.
- Fausto Almeida
- , Julie M. Wolf
- & Arturo Casadevall
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Article
| Open AccessMicrobial volatile communication in human organotypic lung models
There is a need for improved in vitro models of host-microbe interactions in the lung. Here, Barkal et al. present a microscale organotypic model of the human bronchiole for studying pulmonary infection, including volatile compound communication between microbial populations and host cells.
- Layla J. Barkal
- , Clare L. Procknow
- & David J. Beebe
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Article
| Open AccessUnique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA
Memory T cells are essential for combating recurring infection by promoting prompt and effective immune responses. Here the authors show, via system biology approaches, that human CD4 memory T cells contains a CD45RA-rexpressing pool that can be further subsetted by the expression of GPR56 for distinct functionalities.
- Yuan Tian
- , Mariana Babor
- & Bjoern Peters
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Article
| Open AccessKenny mediates selective autophagic degradation of the IKK complex to control innate immune responses
Selective autophagy describes the selective degradation of cellular components upon stress or nutrient deficiency, but whether it modulates innate immunity is unclear. Here the authors show that Drosophila Kenny may be an evolution-selected autophagy receptor for the down-regulation of innate NF-κB activation
- Radu Tusco
- , Anne-Claire Jacomin
- & Ioannis P. Nezis
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Article
| Open AccessBlood meal acquisition enhances arbovirus replication in mosquitoes through activation of the GABAergic system
Transmission of many human viruses depends on replication in their mosquito vectors. Here, Zhu et al. show that glutamic acid digested from the blood meal activates GABA signaling, resulting in suppression of antiviral innate immunity and increased virus replication in mosquitoes.
- Yibin Zhu
- , Rudian Zhang
- & Gong Cheng
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Article
| Open AccessTRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells
LPS is a major component of gram-negative bacterial cell walls, and triggers immune responses in airway epithelium by activating TLR4. Here the authors show that LPS also activates TRPV4, thereby inducing fast defense responses such as nitric oxide production and increased ciliary beating in mice.
- Yeranddy A. Alpizar
- , Brett Boonen
- & Karel Talavera
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Article
| Open AccessModulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization
Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted by the tick Ixodes scapularis. Here, the authors show that a tick secreted protein (PIXR) modulates the tick gut microbiota and facilitates B. burgdorferi colonization.
- Sukanya Narasimhan
- , Tim J. Schuijt
- & Erol Fikrig
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Article
| Open AccessE3 Ubiquitin ligase ZNRF4 negatively regulates NOD2 signalling and induces tolerance to MDP
Prolonged NOD2 ligand engagement induces tolerance and attenuated NOD2 signalling, but the molecular mechanisms leading to this tolerance induction are unclear. Here the authors show that the degradation of a NOD2 adaptor, RIP2, by the E3 ligase ZNRF4 is essential for the down-regulation of NOD2 signalling.
- Pradeep Bist
- , Wan Shoo Cheong
- & Bindu Sukumaran
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Article
| Open AccessMultiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling
MAVS is an essential component of the pathogen-sensing machinery, and functions by forming prion-like filaments. Here the authors show that alternatively translated forms of truncated endogenous MAVS can prevent spontaneous aggregation and degradation in cells to sustain MAVS-mediated immune signalling.
- Nan Qi
- , Yuheng Shi
- & Fajian Hou
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Article
| Open AccessDifferent populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon
T helper 2 (Th2) cell responses are essential for immunity against parasites, but how Th2 response is modulated in the gut is still unclear. Here the authors show that distinct dendritic cell subsets distinguishable by CD11b, CD103 and IRF4 function in the small intestine or colon to promote Th2 responses.
- Johannes U. Mayer
- , Mimoza Demiri
- & Simon W. Milling
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Article
| Open AccessThe PYRIN domain-only protein POP2 inhibits inflammasome priming and activation
Excessive inflammasome activation leads to inflammatory diseases, but how inflammasomes are regulated by PYD-only adaptors is unclear. Here the authors show that the PYD-only protein POP2 inhibits both inflammasome priming and assembly by interfering, respectively, with IκBα activation and NLRP3-ASC interaction.
- Rojo A. Ratsimandresy
- , Lan H. Chu
- & Christian Stehlik
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Article
| Open AccessPyrin-only protein 2 limits inflammation but improves protection against bacteria
Pyrin-only proteins (POPs) are primate-specific negative regulators of inflammasome activation. Here the authors generate transgenic mice expressing POP2 under the control of the human promoter, and show that POP2 is important for balancing antibacterial inflammatory responsesin vivo.
- Sivakumar Periasamy
- , Kristen A. Porter
- & Jonathan A. Harton
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Article
| Open AccessZinc is a potent and specific inhibitor of IFN-λ3 signalling
Lambda interferons (IFNL) are involved in the immune response to viral infection. Here the authors show that zinc can interfere with IFNL signalling, and that in HCV patients the rs12979860 polymorphism regulates blood zinc levels and, subsequently, the hepatic immune response.
- Scott A. Read
- , Kate S. O’Connor
- & Golo Ahlenstiel
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Article
| Open AccessCD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis
CD103+ dendritic cells induce iTreg cells to maintain immune balance in the gut, but how CD40-signalling regulates this process is unclear. Here the authors show that mice with constitutive CD11c-specific CD40-signalling have altered CD103+dendritic cell migration, reduced iTreg cell induction, and fatal colitis.
- Christian Barthels
- , Ana Ogrinc
- & Thomas Brocker
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Article
| Open AccessSplenic differentiation and emergence of CCR5+CXCL9+CXCL10+ monocyte-derived dendritic cells in the brain during cerebral malaria
Cerebral malaria is an often fatal complication ofPlasmodium infection involving accumulation of inflammatory leukocytes in the central nervous system. Here the authors map the development and trafficking of CCR5+ monocyte-derived dendritic cells from the spleen to the brains of Plasmodium bergheiANKA infected mice.
- Isabella C. Hirako
- , Marco A. Ataide
- & Ricardo T. Gazzinelli
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Article
| Open AccessImmune modulation enables a specialist insect to benefit from antibacterial withanolides in its host plant
Certain plants in the nightshade family contain withanolides, defensive chemicals known to be harmful to most insect herbivores. Here, Barthel et al. show that a moth species that is a specialist herbivore of these plants benefits from the compounds by gaining increased immunity to a pathogen.
- Andrea Barthel
- , Heiko Vogel
- & Hanna M. Heidel-Fischer
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| Open AccessHuman TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens
Mucosal-associated invariant T (MAIT) cells sense riboflavin biosynthetic intermediate antigens with a semi-invariant MR1-restricted T-cell receptor (TCR). Here the authors identify a new MR1-restricted TCR that senses cells infected with S. pyogenes, a bacteria unable to biosynthesize riboflavin.
- Erin W. Meermeier
- , Bruno F. Laugel
- & David M. Lewinsohn
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Article
| Open AccessMicrobe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes
Both sterile and microbial injuries lead to rapid neutrophil recruitment to the site of inflammation. Here the authors show that only neutrophils responding to microbial ligands leave inflamed skin and migrate to draining lymph nodes where they stimulate lymphocyte proliferation.
- Henry R. Hampton
- , Jacqueline Bailey
- & Tatyana Chtanova
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Article |
The staphylococcal toxins γ-haemolysin AB and CB differentially target phagocytes by employing specific chemokine receptors
Genes encoding two pore-forming toxins (γ-haemolysins HlgAB and HlgCB) are present in almost all human Staphylococcus aureus isolates. Here Spaan et al.show that HlgAB and HlgCB target different phagocyte types by interacting with specific chemokine receptors and complement receptors, respectively.
- András N. Spaan
- , Manouk Vrieling
- & Thomas Henry