Pathogenesis articles within Nature Communications

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• Article
  29 November 2023 | Open Access

  Dermis resident macrophages orchestrate localized ILC2 eosinophil circuitries to promote non-healing cutaneous leishmaniasis

  Tissue resident macrophages are intricately involved in homeostatic processes but also in tissue repair. Here Lee and colleagues show dermis-resident macrophages are a source of thymic stromal lymphopoietin and CCL24, which act on type 2 innate lymphoid cells and eosinophils respectively, to maintain their M2 properties and promote non-healing cutaneous leishmaniasis.

  • Sang Hun Lee
  • , Byunghyun Kang
  •  & David L. Sacks

• Article
  27 November 2023 | Open Access

  RNA is a key component of extracellular DNA networks in Pseudomonas aeruginosa biofilms

  The roles of extracellular RNAs present in bacterial biofilms are poorly understood. Here, Mugunthan et al. show that specific mRNAs associate with extracellular DNA in the matrix of bacterial biofilms, facilitating the formation of viscoelastic networks.

  • Sudarsan Mugunthan
  • , Lan Li Wong
  •  & Thomas Seviour

• Article
  24 November 2023 | Open Access

  The extrafollicular B cell response is a hallmark of childhood idiopathic nephrotic syndrome

  Although B cell-targeting therapies can provide clinical benefits to children with idiopathic nephrotic syndrome (INS), B lymphocyte subsets have not been extensively studied in this disease. Here, using single-cell RNA sequencing, the authors identify an extrafollicular B cell signature in children with INS.

  • Tho-Alfakar Al-Aubodah
  • , Lamine Aoudjit
  •  & Tomoko Takano

• Article
  24 November 2023 | Open Access

  Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures

  Paediatric high-grade gliomas with MYCN amplification (HGG-MYCN) are rare and highly aggressive. Here, the authors generate a mouse model for HGG-MYCN that can recapitulate the histological and molecular profiles of the human tumours, and perform high-throughput drug screening to identify potential treatment options.

  • Melanie Schoof
  • , Shweta Godbole
  •  & Ulrich Schüller

• Article
  23 November 2023 | Open Access

  SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling

  White adipose tissue is closely associated with energy expenditure and obesity. Here, the authors show that SLC35D3 promotes white adipose tissue browning through the NOTCH1 signalling pathway and SLC35D3 may be a potential therapeutic target for obesity and related complications.

  • Hongrui Wang
  • , Liang Yu
  •  & Yibo Wang

• Article
  17 November 2023 | Open Access

  Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions

  Here, Rueff et al engineered a CRISPRi-based oscillator to rewire capsule production in Streptococcus pneumoniae from its native control. They show that heterogeneity in capsule production is beneficial for fitness in several virulence associated traits.

  • Anne-Stéphanie Rueff
  • , Renske van Raaphorst
  •  & Jan-Willem Veening

• Article
  14 November 2023 | Open Access

  Epidermal growth factor receptor activation is essential for kidney fibrosis development

  Fibrosis is the progressive accumulation of excess extracellular matrix produced by myofibroblasts leading to organ failure. Here the authors show that expression of the Epidermal Growth Factor Receptor (EGFR) increases in interstitial myofibroblasts in human and mouse fibrotic kidneys, and selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins.

  • Shirong Cao
  • , Yu Pan
  •  & Raymond C. Harris

• Article
  14 November 2023 | Open Access

  Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins

  Here, Ning et al report the cellular interactomes of Crimean-Congo haemorrhagic fever virus glycoproteins and uncover a host restriction factor HAX1 that hijacks the viral glycoproteins to mitochondria, disabling progeny virion packaging.

  • Shiyu Dai
  • , Yuan-Qin Min
  •  & Yun-Jia Ning

• Article
  26 October 2023 | Open Access

  A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype

  The neurovirulence determinants of Zika virus remain not fully established. Song et al identified a single K101R substitution in the capsid protein that contributes to the lineage-specific virulence phenotypes.

  • Guang-Yuan Song
  • , Xing-Yao Huang
  •  & Cheng-Feng Qin

• Article
  25 October 2023 | Open Access

  Localized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease

  The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.

  • Zongyuan Liu
  • , Rebecca Ulrich vonBargen
  •  & Laura-Isobel McCall

• Article
  18 October 2023 | Open Access

  Ubiquitin ligase CHFR mediated degradation of VE-cadherin through ubiquitylation disrupts endothelial adherens junctions

  Vascular endothelial cadherin (VE-cadherin), endothelial cell-cell adhesive protein maintains blood vessel barrier integrity and vascular homeostasis. Here, the authors show that infectious bacterial toxin activates ubiquitin ligase CHFR which in turn degrades VEcadherin via ubiquitylation in endothelial cells to cause vascular injury.

  • Chinnaswamy Tiruppathi
  • , Dong-Mei Wang
  •  & Asrar B. Malik

• Article
  13 October 2023 | Open Access

  Gut 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

• Article
  11 October 2023 | Open Access

  SARS-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

• Article
  20 September 2023 | Open Access

  NLRP3 selectively drives IL-1β secretion by Pseudomonas aeruginosa infected neutrophils and regulates corneal disease severity

  Bacterial infection of immune cells can result in engagement of different immunological pathways. Here the authors show that a Pseudomonas aeruginosa type three secretion system exoenzyme is linked to the differential selection of inflammasome usage between macrophages and neutrophils.

  • Martin S. Minns
  • , Karl Liboro
  •  & Eric Pearlman

• Article
  14 September 2023 | Open Access

  Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent

  Breast cancer patients of African ancestry face worse clinical outcomes, so understanding related cellular and molecular features remains critical. Here, the authors show that stromal cells that are particularly enriched in breast cancer patients with African ancestry can trans-differentiate into different lineages and can be transformed into metaplastic carcinoma.

  • Brijesh Kumar
  • , Aditi S. Khatpe
  •  & Harikrishna Nakshatri

• Article
  06 September 2023 | Open Access

  NAD(H) homeostasis underlies host protection mediated by glycolytic myeloid cells in tuberculosis

  Mycobacterium tuberculosis disrupts glycolysis in infected myeloid cells. Here, Pacl et al. show that maximal glycolytic capacity in myeloid cells is essential for host protection from tuberculosis and that NAD(H) homeostasis underlies glycolysis-mediated protection of the host.

  • Hayden T. Pacl
  • , Krishna C. Chinta
  •  & Adrie J. C. Steyn

• Article
  05 September 2023 | Open Access

  Identification 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

• Article
  24 August 2023 | Open Access

  Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype

  Acquired resistance to immune checkpoint inhibitors limits therapeutic success in non-small-cell lung cancer, however, the underpinning immune parameters are largely unknown. Here authors distinguish resistance types based on immune cell infiltration, immune checkpoint molecule and cytokine expression level, using paired samples from patients in the sensitive and in the resistant disease phase.

  • Stefanie Hiltbrunner
  • , Lena Cords
  •  & Alessandra Curioni-Fontecedro

• Article
  08 August 2023 | Open Access

  Spatial transcriptomics analysis of esophageal squamous precancerous lesions and their progression to esophageal cancer

  Understanding the molecular changes in the transition from esophageal squamous precancerous lesions (ESPL) to esophageal squamous cell carcinoma (ESCC) remains essential. Here, the authors analyze ESPL samples using spatial transcriptomics and reveal expression changes in TAGLN2 and CRNN during progression to ESCC.

  • Xuejiao Liu
  • , Simin Zhao
  •  & Zigang Dong

• Article
  26 July 2023 | Open Access

  Neuroinvasion 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

• Article
  22 July 2023 | Open Access

  LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis

  Inhibition of immunocyte infiltration and activation has been suggested to ameliorate hepatic inflammation and fibrosis in nonalcoholic steatohepatitis. Here, the authors show PirB/LILRB2 regulates the migration of macrophages during NASH by binding with ANGPTL8, which is involved in the regulation of NASH development.

  • Dan-Pei Li
  • , Li Huang
  •  & Xue-Feng Yu

• Article
  19 July 2023 | Open Access

  IKK2/NFkB signaling controls lung resident CD8⁺ T cell memory during influenza infection

  CD8⁺ T resident memory (T_RM) 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

• Article
  15 July 2023 | Open Access

  pH-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

• Article
  06 July 2023 | Open Access

  Interplay 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

• Article
  05 July 2023 | Open Access

  Whole genome sequencing identifies genetic variants associated with neurogenic inflammation in rosacea

  Rosacea is a common, multi-factorial chronic inflammatory skin disorder. Here authors provide evidence of genetic predisposition by whole genome sequencing and whole exome sequencing of samples from familial cases, and by recapitulating a recurrent mutation in the LRRC4 gene in a mouse model, they find that neuron-derived vasoactive intestinal peptide is an important pathogenic factor for neurogenic inflammation in rosacea.’

  • Zhili Deng
  • , Mengting Chen
  •  & Ji Li

• Article
  30 June 2023 | Open Access

  Differentiation of IL-26⁺ T_H17 intermediates into IL-17A producers via epithelial crosstalk in psoriasis

  Interleukin 26 (IL-26) has been shown to have antimicrobial and pro-inflammatory effects. Here the authors establish a role for IL-26 in the generation of IL-17A producing Th17 CD4⁺ T cells and suggest it involves epithelial cross talk in skin lesions of psoriasis patients.

  • Anissa Fries
  • , Fanny Saidoune
  •  & Michel Gilliet

• Article
  10 June 2023 | Open Access

  Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

  Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. Here, using genetic data for 1.52 million individuals, the authors identify 25 genes with protein-altering variants exhibiting a strong deficit of homozygosity, suggesting they are essential for successful early development.

  • Asmundur Oddsson
  • , Patrick Sulem
  •  & Daniel F. Gudbjartsson

• Article
  05 June 2023 | Open Access

  Hamster 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

• Article
  03 June 2023 | Open Access

  Intrinsic TGF-β signaling attenuates proximal tubule mitochondrial injury and inflammation in chronic kidney disease

  Chronic kidney disease (CKD) is a disease that irreversibly leads to loss of renal function. Here, the authors demonstrate the beneficial effect of intrinsic TGF-b signaling on mitochondrial function and inflammation in the proximal tubule epithelium in response to kidney injury.

  • Merve Kayhan
  • , Judith Vouillamoz
  •  & Stellor Nlandu Khodo

• Article
  03 June 2023 | Open Access

  Sequential 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

• Article
  29 May 2023 | Open Access

  Fibroblasts 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

• Article
  10 May 2023 | Open Access

  Viral 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

• Article
  29 April 2023 | Open Access

  PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis

  IL-9-producing helper T (T_H9) cells contribute to allergic inflammation. In this study, the authors demonstrate that the transcription factor PPAR-γ regulates T_H9 effector function by promoting glucose metabolism and mTOR signaling in human allergic contact dermatitis.

  • Nicole L. Bertschi
  • , Oliver Steck
  •  & Christoph Schlapbach

• Article
  24 April 2023 | Open Access

  Sample-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

• Article
  20 April 2023 | Open Access

  AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling

  Thoracic aortic aneurysm (TAA) causes many sudden deaths each year, however, no effective drug treatment is available. Here, the authors show that AGGF1 protein therapy attenuates TAA in three different mouse models through integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signalling.

  • Xingwen Da
  • , Ziyan Li
  •  & Qing K. Wang

• Article
  04 April 2023 | Open Access

  Multiplatform 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

• Article
  22 March 2023 | Open Access

  A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth

  The dynamic and temporal changes of host genome architecture during Epstein-Barr virus (EBV) transformation are not well known. Here the authors transform human primary B lymphocyte into lymphoblastoid cell lines (LCLs) with EBV and show that the host 3D genome is rewired to facilitate expression of key oncogenes.

  • Chong Wang
  • , Xiang Liu
  •  & Bo Zhao

• Article
  16 March 2023 | Open Access

  Cryptosporidium 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

• Article
  06 March 2023 | Open Access

  Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model

  The immune response has been suggested to be involved in the pathology of Ménière’s disease. Here the authors implicate serum glucocorticoid-inducible kinase 1 as a regulator of the NLRP3 inflammasome and link to macrophage function in a model of Ménière’s disease pathology.

  • Dao-Gong Zhang
  • , Wen-Qian Yu
  •  & Hai-Bo Wang

• Article
  28 February 2023 | Open Access

  Zika 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

• Article
  23 February 2023 | Open Access

  TEFM variants impair mitochondrial transcription causing childhood-onset neurological disease

  Van Haute et al describe autosomal recessive TEFM variants that impair mitochondrial transcription elongation and reduce the levels of promoter distal mitochondrial RNA transcripts, leading to heterogeneous mitochondrial diseases with a treatable neuromuscular transmission defect.

  • Lindsey Van Haute
  • , Emily O’Connor
  •  & Rita Horvath

• Article
  23 February 2023 | Open Access

  The 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

• Article
  15 February 2023 | Open Access

  Reciprocal 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

• Article
  15 February 2023 | Open Access

  Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

  PREGCARE is a new strategy for families who had a child with a pathogenic de novo mutation, that efficiently identifies couples at higher recurrence risk due to parental mosaicism, while reassuring many others that their recurrence risk is negligible.

  • Marie Bernkopf
  • , Ummi B. Abdullah
  •  & Anne Goriely

• Article
  13 February 2023 | Open Access

  Repair 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

• Article
  11 February 2023 | Open Access

  Distinct 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

• Article
  08 February 2023 | Open Access

  A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis

  Although anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis and generally considered pathogenic, their functional relevance is incompletely understood. In this study, the authors describe an ACPA with a protective effect against antibody-induced arthritis in mice.

  • Yibo He
  • , Changrong Ge
  •  & Rikard Holmdahl

• Article
  02 February 2023 | Open Access

  High-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

• Article
  30 January 2023 | Open Access

  Mechanism 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

• Article
  28 January 2023 | Open Access

  Quantitative 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