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| 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
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| Open AccessSARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition
Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.
- Rachel Erickson
- , Chang Huang
- & Peter D. Sun
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| Open AccessCreating resistance to avian influenza infection through genome editing of the ANP32 gene family
In chickens, influenza A virus relies on host protein ANP32A. Here the authors use CRISPR/Cas9 to generate homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.
- Alewo Idoko-Akoh
- , Daniel H. Goldhill
- & Mike J. McGrew
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| Open AccessHMGB2 regulates the differentiation and stemness of exhausted CD8+ T cells during chronic viral infection and cancer
T cells can become exhausted during chronic virus infection or repeated stimulation by tumour antigens. Here the authors show that High-Mobility Group Box 2 (HMGB2) protein promotes CD8+ T cell memory cell generation in acute viral infection and exhaustion stemness in chronic infection.
- Emily N. Neubert
- , Julia M. DeRogatis
- & Roberto Tinoco
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| Open AccessIdentification of potent and selective N-myristoyltransferase inhibitors of Plasmodium vivax liver stage hypnozoites and schizonts
Developing selective N-myristoyltransferase (NMT) inhibitors has been challenging. Here, the authors describe selective NMT inhibitors that can be used as multistage antimalarials, targeting dormant and developing forms of liver and blood stage.
- Diego Rodríguez-Hernández
- , Kamalakannan Vijayan
- & Morten Grøtli
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| Open AccessNeutrophil metalloproteinase driven spleen damage hampers infection control of trypanosomiasis
Trypanosoma brucei infection is characterised by activation of neutrophil associated genes. Here, Pham et al. further dissect the role neutrophils play in tissue pathology, disease outcome and maintenance of adaptive immunity.
- Hien Thi Thu Pham
- , Stefan Magez
- & Magdalena Radwanska
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| 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
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| Open AccessPersistent symptoms after COVID-19 are not associated with differential SARS-CoV-2 antibody or T cell immunity
Authors utilise a cohort of healthcare workers, infected during the first wave of the SARS-CoV-2 pandemic, to assess symptom persistence and humoral and cellular immunity.
- Daniel M. Altmann
- , Catherine J. Reynolds
- & Rosemary J. Boyton
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| Open AccessLymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice
There is a clinical need for effective and efficacious vaccines for Epstein-Barr virus (EBV) that induce substantive and protective immunity. Here the authors use a combined lymph-node targeted adjuvant and subunit vaccine against EBV and show the induction and effectiveness in a human leukocyte antigen expressing murine model.’
- Vijayendra Dasari
- , Lisa K. McNeil
- & Rajiv Khanna
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| Open AccessNeuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants
Here, Dias de Melo et al. assess the clinical, olfactory, and neuroinflammatory conditions of golden hamsters infected with SARS-CoV-2 wt and VOCs and report that viruses can infect neurons, travel inside axons, and invade the central nervous system.
- Guilherme Dias de Melo
- , Victoire Perraud
- & Hervé Bourhy
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| Open AccessIKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection
CD8+ T resident memory (TRM) cells are important in protection against virus infection and NFκB signalling may function in this process. Here the authors use an inducible transgenic mouse models where T cell intrinsic NFκB levels can be increased or decreased which affects how CD8+ TRM cells seed into the lungs after influenza infection.
- Curtis J. Pritzl
- , Dezzarae Luera
- & Emma Teixeiro
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Article
| Open AccesspH-dependence of the Plasmodium falciparum chloroquine resistance transporter is linked to the transport cycle
PfCRT is a chloroquine resistance transporter from malaria parasite Plasmodium falciparum, which is sensitive to acidic pH. Here, the authors show that residue E207 is critical for pH sensing by PfCRT, using alanine-scanning mutagenesis, MD simulations and drug uptake assays.
- Fiona Berger
- , Guillermo M. Gomez
- & Michael Lanzer
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| Open AccessIntranasal influenza-vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response in hamsters
Understanding the utility of SARS -CoV-2 vaccination platforms and strategies through the emerging pandemic and beyond are critical to understanding the efficacy of such interventions. Here the authors assess nasal delivery of an influenza virus based viral vector for vaccination against SARS-CoV-2 in a hamsters model and assess the induced immunity.
- Liang Zhang
- , Yao Jiang
- & Ningshao Xia
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| Open AccessInterplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability
The combination of host and pathogen diversity can result in variability in disease severity between individuals. Here the authors utilise a model of Streptococcus pyogenes infection and show the impact of human STING genotype and bacterial NADase activity on pathology.
- Elin Movert
- , Jaume Salgado Bolarin
- & Fredric Carlsson
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| Open AccessImmunological imprinting of humoral immunity to SARS-CoV-2 in children
The immune responses to SARS CoV-2 infection in children are less well understood than in adults. Here the authors characterise immune responses to newer omicron lineages and relate these to previous infection with earlier lineages of SARS-CoV-2, implicating a reduced immunogenicity from omicron variants and imprinting from previous virus strains.
- Alexander C. Dowell
- , Tara Lancaster
- & Paul Moss
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| Open AccessMitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response
Mitochondrial function has been linked to immunity but the role of the Krebs’s cycle in regards the immune response is not well characterised. Here the authors show that Krebs’s cycle enzyme ACO2 suppresses immunity via modulation of oxaloacetate and the mitochondrial unfolded protein response.
- Eunah Kim
- , Andrea Annibal
- & Seung-Jae V. Lee
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| Open AccessImmune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection
The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.
- Sunil K. Ahuja
- , Muthu Saravanan Manoharan
- & Weijing He
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| Open AccessHamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2
Heydemann et al. investigate alveolar regeneration mechanisms after SARS-CoV-2 infection in the hamster model, offering insight into the pathomechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).
- Laura Heydemann
- , Małgorzata Ciurkiewicz
- & Federico Armando
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| Open AccessSequential intrahost evolution and onward transmission of SARS-CoV-2 variants
There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.
- Ana S. Gonzalez-Reiche
- , Hala Alshammary
- & Harm van Bakel
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| Open AccessFibroblasts are a site of murine cytomegalovirus lytic replication and Stat1-dependent latent persistence in vivo
Fibroblasts are an established cell type permissive for cytomegalovirus infection. Here the authors identify a population of fibroblast cells that can support murine cytomegalovirus lytic and latent virus infection in vivo and propose STAT1 as critically involved in murine cytomegalovirus latency.
- Katarzyna M. Sitnik
- , Fran Krstanović
- & Luka Čičin-Šain
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| Open AccessSingle cell transcriptomics clarifies the basophil differentiation trajectory and identifies pre-basophils upstream of mature basophils
Single cell sequencing can be used to better characterize immune cell progenitors. Here the authors characterize CLEC12Ahi pre-basophils downstream of pre-basophil and mast cell progenitors (pre-BMPs) but upstream of mature basophils and this population includes basophil progenitors (BaPs).
- Kensuke Miyake
- , Junya Ito
- & Hajime Karasuyama
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| Open AccessViral subversion of selective autophagy is critical for biogenesis of virus replication organelles
Virus triggered lipophagy is important for flaviviral assembly and coordinated by Aup1 and the ubiquitin conjugating enzyme E2. Here, Lan et al further characterise the interplay between these proteins and how they function to modulate selective autophagy and viral replication.
- Yun Lan
- , Sophie Wilhelmina van Leur
- & Sumana Sanyal
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| Open AccessSingle-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation
Zika virus poses a potential threat to male reproductive health but the underlying mechanisms remain obscure. To address this question, the study by Yang et al performs single-cell RNA sequencing with ZIKV-infected mice testes. The authors find that spermatogenic cells are fragile to ZIKV infection and the complement system components produced by infiltrated S100A4 + monocytes/macrophages are crucial for the injury of spermatogenic cells.
- Wei Yang
- , Li-Bo Liu
- & Pei-Gang Wang
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| Open AccessSample-to-answer platform for the clinical evaluation of COVID-19 using a deep learning-assisted smartphone-based assay
The lateral flow assay (LFA) has been considered a rapid test tool but with low sensitivity hampering the precise diagnosis. Here, the authors report bioengineered enrichment tools for LFAs with enhanced sensitivity and specificity that can reinforce LFA’s clinical performance.
- Seungmin Lee
- , Sunmok Kim
- & Jeong Hoon Lee
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| Open AccessRhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Viral infections and exposure to inhaled allergens are linked to asthma onset, exacerbations and progression. Here, the authors used controlled experimental rhinovirus infection in patients with and without asthma, and further assessed in vitro the role of house dust mite allergen combined with rhinovirus and SARS-CoV-2 infection. They discovered that rhinovirus-induced activation of epithelial RIG-I inflammasome supresses antiviral immunity, promotes inflammation during asthma exacerbations and aggravates subsequent infection with SARS-CoV-2, particularly upon house dust mite exposure.
- Urszula Radzikowska
- , Andrzej Eljaszewicz
- & Milena Sokolowska
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| Open AccessHuman CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis
Infection with Streptococcus pyogenes after childbirth can have life threatening consequences. Here, Catton et al. show that the epidemiologically associated bacterial R28 protein targets the human CEACAM1 receptor to facilitate the pathogenesis of bacterial sepsis.
- Erin A. Catton
- , Daniel A. Bonsor
- & Alex J. McCarthy
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| Open AccessA bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3
Innate immune evasion is a key aspect of bacterial pathogenesis. Here, Ta et al identify and characterise EhaF, a bacterial autotransporter that functions to inhibit host innate immunity and promote the colonisation and pathogenesis of enterohemorrhagic Escherichia coli.
- Atri Ta
- , Rafael Ricci-Azevedo
- & Sivapriya Kailasan Vanaja
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| Open AccessTREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques
‘The induction and coordination of immune cells in response to SARS-CoV-2 infection are critical in the immunopathology of COVID-19. Here the authors use a rhesus macaque model of SARS-CoV-2 infection and show key populations of macrophage drive the inflammatory cytokine production in the alveolar space’.
- Amit A. Upadhyay
- , Elise G. Viox
- & Steven E. Bosinger
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| Open AccessMultiplatform analyses reveal distinct drivers of systemic pathogenesis in adult versus pediatric severe acute COVID-19
In this work, authors take a multiomics and microfluidics-based approach to elucidate the mechanism of endothelial damage in critical illness associated with SARS-CoV-2.
- Samuel Druzak
- , Elizabeth Iffrig
- & Cheryl L. Maier
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| 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
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Article
| Open AccessB cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation
Class switch recombination (CSR) is a process by which B cells switch their immunoglobulin isotype and develop pathogen-eliminating antibodies. Here, the authors show that a protein kinase DYRK1A is required for protection from viral infection through the regulation of CSR and effective clonal expansion.
- Liat Stoler-Barak
- , Ethan Harris
- & Ziv Shulman
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| Open AccessControl of human cytomegalovirus replication by liver resident natural killer cells
Natural killer cells play important roles in the immune response to human cytomegalovirus infection. Here the authors implicate donor-derived liver resident natural killer cells in the control of human cytomegalovirus infection by analysis of perfusates derived from human transplant livers.
- Calum Forrest
- , Thomas J. G. Chase
- & Matthew Reeves
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Article
| Open AccessZika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1
Human RNA binding protein Musashi-1 binds various host transcripts as well as Zika virus RNA in neural progenitor cells. Here, Chen et al. characterise the interactions between Musashi-1 and its binding site using a combination of molecular and biophysical methods to shed light on its role in viral neurotropism.
- Xiang Chen
- , Yan Wang
- & Cheng-Feng Qin
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| Open AccessThe cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
A gB/MF59 vaccine candidate for human cytomegalovirus (HCMV) provided partial protection in organ transplant patients. Here, the authors identify antibody responses in trial participants that target virally infected cells to control cell-to-cell spread of HCMV, providing a potential mechanism for the observed protection.
- A. C. Gomes
- , I. A. Baraniak
- & M. B. Reeves
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Article
| Open AccessProlonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys
HIV infection results in the depletion of CD4+ T cells overtime and the loss of coordinated cellular immunity, but how this corresponds to the SIV infected African Green Monkey (AGM) model of non-progressive disease is not known. Here the authors assess the impact of experimental CD4+ T cell depletion in AGM and show that lack of disease progression and resistance to AIDS in this model are independent of CD4+ T cell loss.
- Quentin Le Hingrat
- , Paola Sette
- & Ivona Pandrea
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| Open AccessReciprocal modulation of ammonia and melanin production has implications for cryptococcal virulence
Cryptococcus neoformans has numerous described virulence mechanisms including urease secretion and melanization. Here, Baker and Casadevall, describe the reciprocal relationship between these two factors and their contribution to infection.
- Rosanna P. Baker
- & Arturo Casadevall
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Article
| Open AccessRepair of airway epithelia requires metabolic rewiring towards fatty acid oxidation
Airway epithelial repair, a key process in the recovery from lung injury, requires a metabolic shift from glycolysis to fatty acid oxidation (FAO). Pharmacological FAO promotion enhances epithelial differentiation, suggesting new therapeutic options.
- Stefania Crotta
- , Matteo Villa
- & Andreas Wack
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Article
| Open AccessDistinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19
Infection with SARS-CoV-2 has been linked with substantive inflammation, lung pathology and development of COVID-19. Here the authors spatially associate CCL18 and CCL21 in distinct tissue niches with lung pathology of severe COVID-19.
- Ronja Mothes
- , Anna Pascual-Reguant
- & Anja E. Hauser
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Article
| Open AccessMyristic acid as a checkpoint to regulate STING-dependent autophagy and interferon responses by promoting N-myristoylation
Stimulator of interferon gene (STING) plays critical roles in the host response to infection and in the production of interferon. Here the authors suggests myristic acid is involved in the homeostatic balancing of STING dependent autophagy and the interferon response.
- Mutian Jia
- , Yuanyuan Wang
- & Wei Zhao
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Article
| Open AccessHigh-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection
Here, by high-resolution SARS-CoV-2 sequencing, genomic and transcriptomic analyses from tissue samples, Normandin et al. investigate viral dynamics in fatal cases of COVID-19, revealing persistent infection in distinct anatomical sites, including the heart and testis.
- Erica Normandin
- , Melissa Rudy
- & Isaac H. Solomon
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Article
| Open AccessMechanism of regulation of the Helicobacter pylori Cagβ ATPase by CagZ
Cagβ is an ATPase in the H. pylori CagType4 secretion system essential for delivering the CagA effector to host cells. Here, authors present crystal structures of hexameric apo-Cagβ and Cagβ trapped in the monomeric state by its regulator CagZ, uncovering the regulatory mechanisms of Cagβ.
- Xiuling Wu
- , Yanhe Zhao
- & Yunkun Wu
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Article
| Open AccessQuantitative dose-response analysis untangles host bottlenecks to enteric infection
Here, using Citrobacter rodentium colonization of mice as a model, the authors characterize the impact of pathogen dose on the number of bacteria that initiate infection in the mouse gut, providing a framework for quantifying the host bottlenecks that eliminate pathogens to protect from infection.
- Ian W. Campbell
- , Karthik Hullahalli
- & Matthew K. Waldor
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Article
| Open AccessKaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs
Viruses rely on the translational machinery of the host cell to synthesis viral proteins. We show that KSHV manipulates the composition of host cell ribosomes creating a specialised ribosome to specifically translate viral mRNAs.
- James C. Murphy
- , Elena M. Harrington
- & Adrian Whitehouse
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| Open AccessTranscriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Although myeloid cell dysfunction has been observed in COVID-19, the underlying mechanisms remain incompletely understood. Here, the authors demonstrate that monocytes from patients with mild to moderate COVID-19 show a blunted innate immune response and a pro-thrombotic signature following secondary SARS-CoV-2 challenge.
- Allison K. Maher
- , Katie L. Burnham
- & Margarita Dominguez-Villar
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Article
| Open AccessMicrobiome-mediated fructose depletion restricts murine gut colonization by vancomycin-resistant Enterococcus
Vancomycin-resistant Enterococcus (VRE) represents a major threat for patients’ health. Here, using a mouse model, the authors show that specific commensals restrict VRE gut colonization through depletion of fructose, a nutrient source that boosts VRE growth in vivo.
- Sandrine Isaac
- , Alejandra Flor-Duro
- & Carles Ubeda
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Article
| Open AccessSeroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018
Hand, foot and mouth disease, caused by enterovirus A71 (EV-A71) infection, is common in children in China. Here, the authors estimate EV-A71 incidence and seroprevalence using data from two longitudinal cohorts and find that, despite high infection rates, a large proportion of children under 6 are susceptible.
- Juan Yang
- , Qiaohong Liao
- & Hongjie Yu
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Article
| Open AccessAlveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death
Alveolar macrophages (AM) in the lungs maintain surfactant during homeostasis and respond to infectious pathogens. Here the authors show that in the absence of NKR-P1B, pneumococcal infection is more severe because KO AM have increased rates of lipid surfactant uptake and reduced anti-microbial function.
- Michal Scur
- , Ahmad Bakur Mahmoud
- & Andrew P. Makrigiannis
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Article
| Open AccessGut to lung translocation and antibiotic mediated selection shape the dynamics of Pseudomonas aeruginosa in an ICU patient
In this paper the authors show that the pathogenic bacterium Pseudomonas aeruginosa migrates between the gut and lungs of an ICU patient, and that differential evolutionary responses to antibiotic treatment occur in these organs.
- Rachel M. Wheatley
- , Julio Diaz Caballero
- & R. Craig MacLean
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Article
| Open AccessYAP promotes cell-autonomous immune responses to tackle intracellular Staphylococcus aureus in vitro
Growing evidence indicates that YAP/TAZ transcriptional regulators promote autophagy. Here, the authors characterize the role of YAP against Staphyloccocus aureus infection of synovial organoids and describe the role staphylococcal toxins have in antagonizing YAP-mediated functions.
- Robin Caire
- , Estelle Audoux
- & Paul O. Verhoeven