Featured
-
-
Article
| Open AccessDefective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome
Primary antiphospholipid syndrome (PAPS) is a clotting disorder attributed to autoreactive antibodies produced by B cells. Here the authors show, using single cell omics and B cell repertoire data, that autoreactive B cells originate from the natural B cell repertoire and escape germinal center selection to persist in PAPS patient via potential dysregulation of mTORC1 and MYC pathways.
- Yannick Dieudonné
- , Raquel Lorenzetti
- & Vincent Gies
-
Article
| Open AccessMechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression
Crystalline silica particle exposure in the airways can lead to lung silicosis and progressive fibrosis. Here the authors use mouse silicosis models to show mechanics activated fibroblasts promote conversion of ILC2 to ILC1-like cells pulmonary fibrosis and that this is associated with a Notch3-IL-18 signalling pathway.
- Yangyang He
- , Fan Yang
- & Chao Li
-
Article
| Open AccessAltered genomic methylation promotes Staphylococcus aureus persistence in hospital environment
In this study, authors examine Staphylococcus aureus adaptability in hospitals, highlighting how a lineage evolved to reversibly suppress Agr, enhancing antibiotic resistance and colonization.
- Yuriko Yamazaki
- , Tomoka Ito
- & Yuumi Nakamura
-
Article
| Open AccessInduction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade
Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis.
- Mayra Cruz Tleugabulova
- , Sandra P. Melo
- & Maximilian Nitschké
-
Article
| Open AccessClassification of distinct tendinopathy subtypes for precision therapeutics
This study classifies rotator cuff tendinopathy into three distinct subtypes that include a hypoxic atrophic, an inflammatory proliferative with white appearance and an inflammatory proliferative with red appearance subtype. Using both clinical data and animal models, the research reveals that glucocorticoid is only effective in treating the latter inflammatory proliferative subtype that has the highest level of neovascularization.
- Chenqi Tang
- , Zetao Wang
- & Weiliang Shen
-
Article
| Open AccessHumans without a sense of smell breathe differently
Humans use their nose to both smell and to breath, and respiratory patterns are known to be impacted by odors. Here, the authors applied a wearable respiratory logger to people without a sense of smell, and found that they breath differently. They suggest that this altered breathing may affect health, emotion and cognition.
- Lior Gorodisky
- , Danielle Honigstein
- & Noam Sobel
-
Article
| Open AccessHEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status
It’s poorly understood how renal manifestations develop in HEV infection in patients. Here, the authors observe glomerular accumulation of the viral protein ORF2 in complex with host IgG in immunocompromised patients with chronic or acute HEV infection who developed glomerulonephritis.
- Anne-Laure Leblond
- , Birgit Helmchen
- & Achim Weber
-
Article
| Open AccessAnnexin A2 promotes proliferative vitreoretinopathy in response to a macrophage inflammatory signal in mice
Proliferative vitreoretinopathy (PVR) is a vision-threatening response to ocular injury, in which retinal cells secrete tractional, scar-forming proteins. Here, the authors show that antibody blockade of either Annexin A2 or its inducer, macrophage inflammatory protein-1, prevents PVR in mice.
- Min Luo
- , Dena Almeida
- & Katherine A. Hajjar
-
Article
| Open AccessSingle-cell transcriptomics reveals aberrant skin-resident cell populations and identifies fibroblasts as a determinant in rosacea
Rosacea is a common chronic inflammatory skin disorder mainly affecting the central face. Here, a single-cell atlas of facial skin from rosacea patients and healthy individuals reveals the molecular and cellular changes in skin-resident cell populations and identifies fibroblasts as a determinant in rosacea development.
- Mengting Chen
- , Li Yang
- & Ji Li
-
Article
| Open AccessSingle-cell RNA sequencing reveals the pro-inflammatory roles of liver-resident Th1-like cells in primary biliary cholangitis
Primary biliary cholangitis is a chronic autoimmune disease critically linked to immunological dysregulation but the local immune-pathogenesis is poorly understood. Here the authors present single cell transcriptomic characterisation of primary biliary cholangitis and implicates Th1 like cells in a murine model.
- Ciliang Jin
- , Penglei Jiang
- & Yida Yang
-
Article
| Open AccessNur77 protects the bladder urothelium from intracellular bacterial infection
Recent research has found that a protein, Nur77, helps detect the bacterial product lipopolysaccharide inside cells. In this study, authors show that Nur77 helps protect the bladder from infections caused by a common bacterium, Escherichia coli, which leads to urinary tract infections.
- Christina A. Collins
- , Chevaughn Waller
- & Nicole M. Gilbert
-
Article
| Open AccessShared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children
Severe febrile illnesses in children may be various in presentation and aetiology but involve immune dysfunction amenable to immunomodulation. Here, the authors identify shared neutrophil and T cell dysfunction and a distinct interferon signature in critically ill children with severe febrile illness.
- Harsita Patel
- , Michael J. Carter
- & Leire Estamiana Elorieta
-
Article
| Open AccessImmune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis
Antineutrophil cytoplasmic antibody (ANCA) is currently treated with broad-spectrum immune suppressive drugs. Here the authors decipher inflammatory niches in the kidney of patients with ANCA-GN by combining spatial and single-cell transcriptomics to identify ustekinumab as a promising treatment option and successfully treat four ANCA-GN patients.
- Jonas Engesser
- , Robin Khatri
- & Ulf Panzer
-
Article
| Open AccessA mouse protozoan boosts antigen-specific mucosal IgA responses in a specific lipid metabolism- and signaling-dependent manner
Immunoglobulin A (IgA) is an important part of the mucosal immune response. Here, the authors show that an intestinal commensal protist can enhance mucosal IgA production upon vaccination and that this involves the accumulation of free arachidonic acid in the intestinal lumen.
- Yanbo Kou
- , Shenghan Zhang
- & Yugang Wang
-
Article
| Open AccessPrion protein alters viral control and enhances pathology after perinatal cytomegalovirus infection
The role of cellular prion protein (PrP) during CMV infection in newborns is not entirely clear. Here, the authors show that CMV-induced PrP release mediated by ADAM10 shedding impairs the neonatal antiviral response in mice by compromising CD8 T-cells leading to higher viral titers and more severe disease outcome.
- Dubravka Karner
- , Daria Kvestak
- & Tihana Lenac Rovis
-
Article
| Open AccessMycobacterium tuberculosis cough aerosol culture status associates with host characteristics and inflammatory profiles
Using cough-generated aerosol cultures, authors probe the inflammatory markers and epidemiological characteristics of individuals with pulmonary tuberculosis, in association with infection state.
- Videlis Nduba
- , Lilian N. Njagi
- & David J. Horne
-
Article
| Open AccessThe artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular quiescence/senescence and drug resilience
Artemisinin can induce dormant Plasmodium falciparum forms likely resulting in treatment failure. Here the authors characterize the transcriptome, viability, drug sensitivities, and cellular ultrastructure of dormant parasites after a ~ 5-day maturation process and demonstrate hallmarks of cellular quiescence and senescence.
- Jaishree Tripathi
- , Michal Stoklasa
- & Zbynek Bozdech
-
Article
| Open AccessMacrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice
Here the authors investigate the involvement of the immune modulator ILF3 in abdominal aortic aneurysm, showing that macrophage ILF3 promotes aneurysm progression by increasing NF-kB activity and inhibiting Keap1-Nrf2 signaling.
- Zhao-yang Wang
- , Jie Cheng
- & Ming-xiang Zhang
-
Article
| Open AccessRapid intra-host diversification and evolution of SARS-CoV-2 in advanced HIV infection
High-throughput, single-copy sequencing of SARS-CoV-2 spike in a longitudinal cohort of people with and without HIV infection demonstrates striking intra-host diversity and adaptive evolution of SARS-CoV-2 in people with advanced HIV infection.
- Sung Hee Ko
- , Pierce Radecki
- & Eli A. Boritz
-
Article
| Open AccessAlveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation
Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in type 2 alveolar epithelial (AT2) cells is thought to aggravate alveolar inflammation in acute lung injury. Here, the authors show that the mtLCFAO rate limiting enzyme CPT1a is decreased in AT2 cells in acute respiratory distress syndrome, highlighting the role of mtLCFAO in immunometabolism in this context.
- Kuei-Pin Chung
- , Chih-Ning Cheng
- & Chong-Jen Yu
-
Article
| Open AccessMolecular epidemiology and population immunity of SARS-CoV-2 in Guangdong (2022–2023) following a pivotal shift in the pandemic
Release of the zero-COVID policy in China in late 2022 led to two large Omicron-driven waves of infection in 2023. Here, the authors analyze virus genomes and serology data from before and after the two waves and describe changes in virus lineage distribution and age-specific antibody responses.
- Zhencui Li
- , Pei Hu
- & Jing Lu
-
Article
| Open AccessDynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs
Antibiotic treatments for tuberculous meningitis, the deadliest form of tuberculosis, are not optimized. Here, PET in human and animal studies is used to measure the biodistribution of several antibiotics to develop optimized regimens for drug-resistant tuberculous meningitis.
- Xueyi Chen
- , Bhavatharini Arun
- & Sanjay K. Jain
-
Article
| Open AccessRNA interactome of hypervirulent Klebsiella pneumoniae reveals a small RNA inhibitor of capsular mucoviscosity and virulence
By performing a global RNA-RNA interactome analysis in hypervirulent Klebsiella pneumoniae, the authors identify the small RNA ArcZ targets many capsule genes and a key virulence factor MlaA, inhibiting Klebsiella infection and pathogenesis in mice.
- Kejing Wu
- , Xingyu Lin
- & Yanjie Chao
-
Article
| Open AccessRestriction of arginine induces antibiotic tolerance in Staphylococcus aureus
Utilising proteomic and transposon sequencing screens, Freiberg et al. identified arginine metabolism enzymes that impact tolerance to antibiotics in Staphylococcus aureus, including in animal models of skin and bone infections.
- Jeffrey A. Freiberg
- , Valeria M. Reyes Ruiz
- & Eric P. Skaar
-
Review Article
| Open AccessVentilator-associated pneumonia: pathobiological heterogeneity and diagnostic challenges
Ventilator-associated pneumonia (VAP) is a nosocomial infection that significantly affects critically ill patients undergoing mechanical ventilation in the Intensive Care Unit (ICU). This review presents the diagnostic challenges associated with VAP in ICU.
- Fiona Howroyd
- , Cyril Chacko
- & Tonny Veenith
-
Article
| Open AccessLoss-of-function mutations in Keratin 32 gene disrupt skin immune homeostasis in pityriasis rubra pilaris
Pityriasis rubra pilaris (PRP) is a chronic immune‐mediated papulosquamous dermatosis and is caused by dysregulation of keratinocytes. Here the authors identify keratin 32 (KRT32) mutations associated with PRP which results in the inhibitory function of KRT32 towards NF-kB signalling and IKK complex formation being reduced.
- Peidian Shi
- , Wenjie Chen
- & Furen Zhang
-
Article
| Open AccessTargeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses
Here, Johnson et al show that bacterial pneumonia induces an interaction between the ubiquitin E3 ligase subunit FBX024 and the mitochondrial protein DARS2 to modulate host immune responses.
- Benjamin S. Johnson
- , Daniela Farkas
- & Rama K. Mallampalli
-
Article
| Open AccessControlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas
Hookworm infection remains a threat to public health where economic factors restrict treatment and lack of effective vaccination have limited successful therapeutic control which results in reinfection in endemic areas. Here the authors use a controlled human hookworm infection model and use high dimensional single cell profiling to show that plasmacytoid dendritic cells and regulatory T cells profiles that resemble those seen during natural infections in endemic areas.
- Mikhael D. Manurung
- , Friederike Sonnet
- & Maria Yazdanbakhsh
-
Article
| Open AccessCompartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes
Altered redox biology causes mitochondrial dysfunction, yet mechanisms and implications vary. Here, the authors identify 15 lipoxygenase-linked mitochondrial ferroptosis and mitophagy driving epithelial cell differentiation and asthma outcomes.
- Kazuhiro Yamada
- , Claudette St. Croix
- & Sally E. Wenzel
-
Article
| Open AccessHeterogeneity in lung macrophage control of Mycobacterium tuberculosis is modulated by T cells
Both T cells and lung macrophages are involved in the control of lung tuberculosis infection. Here the authors examine the dependence of the lung macrophage response upon the presence of T cells and show that CD4 and CD8 T cells promote the elimination of M.Tb in alveolar macrophages but have less impact on monocyte-derived macrophages.
- Rocky Lai
- , Travis Williams
- & Samuel M. Behar
-
Article
| Open AccessBiomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa
In this study, by analysing immune biomarkers in a cohort of people with advanced HIV, the authors show that elevated levels of some biomarkers at baseline were associated with either increased (CRP, IFN-ƴ, IL-6 and IP-10) or decreased (IL-23, IL-2 and RANTES) likelihood of all-cause mortality.
- Victor Riitho
- , Roisin Connon
- & Andrew J. Prendergast
-
Article
| Open AccessMycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs
Gosain et al.’s work aims to enhance understanding of the contribution of MenT3 and MenT4 toxins belonging to MenAT TA systems to the physiology and pathogenesis of Mycobacterium tuberculosis. The authors show that strains lacking these proteins is attenuated and confers protection in vivo.
- Tannu Priya Gosain
- , Saurabh Chugh
- & Ramandeep Singh
-
Article
| Open AccessMyelin-reactive B cells exacerbate CD4+ T cell-driven CNS autoimmunity in an IL-23-dependent manner
B cells are crucial in multiple sclerosis (MS) pathology but the mechanisms are incompletely understood. In a mouse model of MS, the authors show that B cells make IL-23, and that IL-23 invokes meningeal inflammation and CNS presence of T peripheral helper cells.
- Mohamed Reda Fazazi
- , Prenitha Mercy Ignatius Arokia Doss
- & Manu Rangachari
-
Article
| Open AccessEnvironmental and genetic regulation of Streptococcus pneumoniae galactose catabolic pathways
Bacterial catabolism of galactose can occur via the tagatose pathway and/or the Leloir pathway. Here, the authors show that galactose utilization potentiates virulence of the pathogen Streptococcus pneumoniae, and the two pathways are induced by different environmental and chemical factors.
- Banaz O. Kareem
- , Ozcan Gazioglu
- & Hasan Yesilkaya
-
Article
| Open AccessSingle-cell and spatially resolved interactomics of tooth-associated keratinocytes in periodontitis
Here, Easter et al. generate a single-cell atlas of human periodontium including sulcular and junctional keratinocytes. Cell-cell communication analysis is used to predict keratinocyte-specific immune cell interactions.
- Quinn T. Easter
- , Bruno Fernandes Matuck
- & Kevin M. Byrd
-
Article
| Open AccessPotential pandemic risk of circulating swine H1N2 influenza viruses
Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.
- Valerie Le Sage
- , Nicole C. Rockey
- & Seema S. Lakdawala
-
Article
| Open AccessThymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers
Developing Type I photosensitizers (PSs) is vital for tackling hypoxic intolerance of photodynamic therapy in the hypoxic microenvironment, but elusive due to the lack of a general molecular design strategy. Here the authors report a universal and simple method to covert traditional Type II PSs to Type I PSs.
- Jiahao Zhuang
- , Guobin Qi
- & Bin Liu
-
Article
| Open AccessNeutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure
This study reports training by lipopolysaccharide to expand neutrophils expressing the anti-bacterial galectin-3 protein defending mice from a lethal bacterial infection, a similar signature associated with survivors of respiratory failure in humans.
- Sudipta Das
- , Tomasz W. Kaminski
- & Prabir Ray
-
Article
| Open AccessHIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes
Despite effective antiviral drugs, HIV-1 transcripts can be found in extracellular vesicles (EVs) in people living with HIV-1. Comparing EVs from serum and cerebrospinal fluid (CSF), the authors show compartmentalized defective viral transcripts that are enriched in the CSF and corelate with cognitive dysfunction.
- Catherine DeMarino
- , Julia Denniss
- & Avindra Nath
-
Article
| Open AccessDisruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis
Macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is implicated in a range of immunopathology. Here the authors show TIGAR drives inflammation and sepsis via activation of TAK1 and that disruption of TIGAR-TAK1 interaction in a murine model of sepsis reduces immunopathology.
- Dongdong Wang
- , Yanxia Li
- & Jingjing Ben
-
Article
| Open AccessMycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine
In this work, authors mechanistically investigate the reduced induction of antimicrobial peptides in Mycobacterium tuberculosis infected macrophages.
- Cheng Peng
- , Yuanna Cheng
- & Lin Wang
-
Article
| Open AccessThe vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans
The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans. Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs.
- Yu Liu
- , Ruina Wang
- & Lan Yan
-
Article
| Open AccessLoss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice
Knowledge of pathogenesis mechanisms and effective treatments for viral myocarditis is lacking. Here, Wang et al show that loss of TRIM29 and PERK inhibitor mitigate viral myocarditis by attenuating PERK-driven ER stress and ROS responses in male mice.
- Junying Wang
- , Wenting Lu
- & Junji Xing
-
Article
| Open AccessPD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models.
- John TCHEN
- , Quentin SIMON
- & Nicolas CHARLES
-
Article
| Open AccessThe IL-33/ST2 axis is protective against acute inflammation during the course of periodontitis
Current animal models of periodontitis are biased towards sample collection from gingival tissue, while other periodontal structures may play similarly important role in the initiation and maintenance of inflammation. Here authors present a model that enables a more comprehensive and longitudinal assessment of periodontal tissues, which points to a pivotal role for the peri-root tissues and an IL-33/ST2 axis in the pathogenesis.
- Anhao Liu
- , Mikihito Hayashi
- & Tomoki Nakashima
-
Article
| Open AccessFibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI
Catheter-associated urinary tract infections can often lead to secondary bloodstream infections, and catheter-induced bladder inflammation. In this work, authors utilise murine models to probe defective fibrinolysis drives extravascular fibrin formation, potentially predisposing hosts to severe CAUTI.
- Jonathan J. Molina
- , Kurt N. Kohler
- & Ana L. Flores-Mireles
-
Article
| Open AccessExpression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease
IgG4-related disease is a fibro-inflammatory disorder, characterized by infiltration of IgG4 producing plasma cells in the target organs. Here authors show that the affected B cells express less ubiquitin-specific protease 25 (USP25), and this results in activation of multiple pathways involved in cytoskeleton reorganization, inflammation and energy metabolism, which might govern disease pathogenesis.
- Panpan Jiang
- , Yukai Jing
- & Chaohong Liu
-
Article
| Open AccessMutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance
Mutations in mexZ, encoding a negative regulator of efflux pump genes, are frequently acquired by Pseudomonas aeruginosa during early lung infection, but do not confer high antibiotic resistance as measured in lab tests. Here, Laborda et al. show that mexZ mutations affect quorum sensing pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within tissues.
- Pablo Laborda
- , Signe Lolle
- & Helle Krogh Johansen
-
Article
| Open AccessParechovirus infection in human brain organoids: host innate inflammatory response and not neuro-infectivity correlates to neurologic disease
In comparison to PeV-A1, infection with PeV-A3 is associated with neurological illness in infants. Here, using brain organoids, the authors suggest that the innate inflammatory response as the underlying reason, and not replication kinetics.
- Pamela E. Capendale
- , Inés García-Rodríguez
- & Katja C. Wolthers