Pathogenesis articles within Nature Communications

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  • Article
    | Open Access

    Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations. Here the authors develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection.

    • Yun Heacock-Kang
    • , Ian A. McMillan
    •  & Tung T. Hoang

  • Article
    | Open Access

    Favipiravir has broad-spectrum antiviral activity against a variety of RNA viruses. Here the authors investigate the safety, pharmacokinetics and anti-SARS-CoV-2 efficacy of different drug dosage in the a Syrian hamster model of infection and, combined with genetic analyses, they show that Favipiravir at high doses decrease viral infectivity while inducing the emergence of mutations in viral genomes, decreasing fitness.

    • Jean-Sélim Driouich
    • , Maxime Cochin
    •  & Antoine Nougairède

  • Article
    | Open Access

    Mutations in ENT3, encoded by SLC29A3, result in anaemia and erythroid hypoplasia, suggesting roles in erythropoiesis. Here the authors show that ENT3 acts as a lysosomal bile acid transporter, and mutation compromises taurine conjugated bile acid transport in erythroid progenitors leading to ER stress, and anaemia.

    • Avinash K. Persaud
    • , Sreenath Nair
    •  & Rajgopal Govindarajan

  • Article
    | Open Access

    Inflammatory bowel diseases are heterogeneous, and little is known about how underlying genetic variation can affect their development. Here, the authors report that intestinal inflammation modulates the effect of host genetics on the gut mucosal expression of 190 genes in the context of inflammatory bowel diseases.

    • Shixian Hu
    • , Werna T. Uniken Venema
    •  & Rinse K. Weersma

  • Article
    | Open Access

    Spores produced by Clostridioides difficile during infection are important for the recurrence of the disease. Here, Castro-Córdova et al. show that the spores gain entry into the intestinal mucosa via pathways dependent on host fibronectin and vitronectin, and spore entry inhibition leads to reduced recurrence of infection in a mouse model.

    • Pablo Castro-Córdova
    • , Paola Mora-Uribe
    •  & Daniel Paredes-Sabja

  • Article
    | Open Access

    Infections with bacteria of the genus Sarcina are associated with gastric diseases of unclear etiology. Here, Owens et al. show that infection with a distinct Sarcina species is strongly associated with a lethal disease that affects sanctuary chimpanzees in Sierra Leone.

    • Leah A. Owens
    • , Barbara Colitti
    •  & Tony L. Goldberg

  • Article
    | Open Access

    Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.

    • Yihua Zhang
    • , Manman Li
    •  & Dapeng Yan

  • Article
    | Open Access

    Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease.

    • David R. Sweet
    • , Neelakantan T. Vasudevan
    •  & Mukesh K. Jain

  • Article
    | Open Access

    Necrotizing Enterocolitis (NEC) is an untreatable intestinal disease in infants. Here the authors show that human and experimental mouse NEC is associated with altered toll-like receptor expression in the intestine, enhanced Th17/type 3 polarization in adaptive immune and innate lymphoid cells, dysregulated microbiota, and reduced interleukin-37 signaling.

    • Steven X. Cho
    • , Ina Rudloff
    •  & Marcel F. Nold

  • Article
    | Open Access

    The immunopathological features of SARS-CoV-2 infection in the lungs remain unclear. Here, the authors provide a comprehensive characterization of post mortem lung tissues of COVID-19 patients and find two distinct patterns characterized by differential expression of interferon stimulated genes (ISGs), which correlate to viral loads, cytokines, lung damage and time of hospitalization, suggesting ISG profiles to mark disease progression

    • Ronny Nienhold
    • , Yari Ciani
    •  & Kirsten D. Mertz

  • Article
    | Open Access

    The pathogenesis of Streptococcus pyogenes (GAS) causing scarlet fever has been associated with the presence of prophages, such as ΦHKU.vir, and their products. Here, the authors characterize the exotoxins SpeC and Spd1 of ΦHKU.vir and show these to act synergistically to facilitate nasopharyngeal colonization in mice.

    • Stephan Brouwer
    • , Timothy C. Barnett
    •  & Mark J. Walker

  • Article
    | Open Access

    Inflammasome activation may contribute to type 2 diabetes, but whether targeting inflammasome is beneficial is unclear. Here the authors show that repurposing nucleoside reverse transcriptase inhibitors for inhibiting inflammasome activation is associated with reduced diabetes development in people and improves insulin sensitivity in experimental settings.

    • Jayakrishna Ambati
    • , Joseph Magagnoli
    •  & Bradley D. Gelfand

  • Article
    | Open Access

    HMGB1 is an inflammatory mediator released by a variety of cell types. Here, the authors show that unlike IL-1β, HMGB1 is released non-specifically following cell lysis.

    • Allen Volchuk
    • , Anna Ye
    •  & Neil M. Goldenberg

  • Article
    | Open Access

    Familial carpal tunnel syndrome (CTS) is common, but causal genes are not characterized. Here the authors report two CTS-related mutations in two large families that impair secretion of COMP in tenocytes, leading to ER stress-induced unfolded protein response, inflammation and fibrosis in patients and mouse models.

    • Chunyu Li
    • , Ni Wang
    •  & Bo Gao

  • Article
    | Open Access

    It is unclear whether 2D metal dichalcogenides (TMD) alone can cause ferroptotic cell death. Here, the authors show TMD nanosheets induced ferroptosis in mammalian cell lines and in a mouse model after aspiration of TMD materials into lungs, causing ferroptotic cell death.

    • Shujuan Xu
    • , Huizhen Zheng
    •  & Ruibin Li

  • Article
    | Open Access

    COVID-19 is a serious pandemic threat to public health, but insights on the pathophysiological and immunological conditions are only emerging. Here the authors use multi-color flow cytometry to characterize CD4+ and CD8+ T cells in peripheral blood from 39 COVID-19 patients in Italy to report altered T cell activation, function and polarization.

    • Sara De Biasi
    • , Marianna Meschiari
    •  & Andrea Cossarizza

  • Article
    | Open Access

    Retinal vein occlusion can cause blindness, and features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here the authors report a non-apoptotic role of endothelial caspase-9 in regulating blood-retina barrier integrity and neuronal survival, which can be therapeutically targeted in a mouse model of retinal vein occlusion.

    • Maria I. Avrutsky
    • , Crystal Colón Ortiz
    •  & Carol M. Troy

  • Article
    | Open Access

    Zika virus (ZIKV) infection of pregnant women is associated with pregnancy loss and birth defects, but molecular insights for the aetiology are scarce. Here the authors show that ZIKV reprograms the host lipidome to facilitate viral replication, induce mitochondria dysfunction, and cause immune imbalance, thereby identifying a potential target for ZIKV therapy.

    • Qian Chen
    • , Jordi Gouilly
    •  & Nabila Jabrane-Ferrat

  • Article
    | Open Access

    ARID1A, which is often mutated in human endometrial cancer, is a component of the SWI/SNF chromatin remodelling complex. Here, the authors show that Arid1a mutations in the mouse endometrium and primary human endometrial epithelial cells cause widespread reprogramming of gene transcription and result in a loss of response to TGFβ.

    • Yohan Suryo Rahmanto
    • , Wenjing Shen
    •  & Ie-Ming Shih

  • Article
    | Open Access

    Ultrasensitive methods for detection of biomarkers for infectious disease are needed for diagnosing, monitoring and targeting treatment. Here the authors develop a digital assay for inflammatory markers, bacterial DNA and antibotic-resistance genes and apply it to characterise asthma patients and predict mortality from septic shock.

    • M. Fatih Abasıyanık
    • , Krysta Wolfe
    •  & Savaş Tay

  • Article
    | Open Access

    The mechanisms behind the high invasiveness of Streptococcus pneumoniae serotype 1 are unclear. Here, Jacques et al. show that this feature is due to overproduction and rapid release of pneumolysin, which induces cytotoxicity and breakdown of tight junctions, allowing rapid bacterial dissemination from the respiratory tract into the blood.

    • Laura C. Jacques
    • , Stavros Panagiotou
    •  & Aras Kadioglu

  • Article
    | Open Access

    Metaplastic breast carcinoma (MBC) is among the most aggressive subtypes of triple-negative breast cancer (TNBC) but the underlying proteome profiles are unknown. Here, the authors characterize the protein signatures of human MBC tissue samples and their relationship to TNBC and normal breast tissue.

    • Sabra I. Djomehri
    • , Maria E. Gonzalez
    •  & Celina G. Kleer

  • Article
    | Open Access

    Around half of the heritability underpinning familial high-grade serous ovarian carcinoma remains unidentified. Here, the authors show that extremely rare protein encoding loss-of-function variants, with a high degree of genetic heterogeneity, may account for some of this missing heritability.

    • Deepak N. Subramanian
    • , Magnus Zethoven
    •  & Ian G. Campbell

  • Article
    | Open Access

    Reperfusion injury following myocardial ischemia is aggravated by inflammation and platelet–neutrophil complex formation. Here the authors show that semaphorin 7A binds to platelet GPIb, enhancing platelet–neutrophil interaction and increasing post-ischemic myocardial tissue injury, and that blockage of semaphorin 7A is protective.

    • David Köhler
    • , Tiago Granja
    •  & Peter Rosenberger

  • Article
    | Open Access

    Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and epitope profiling.

    • Samantha D. Praktiknjo
    • , Benedikt Obermayer
    •  & Nikolaus Rajewsky

  • Article
    | Open Access

    Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

    • Pilar Cacheiro
    • , Violeta Muñoz-Fuentes
    •  & Coleen Kane

  • Article
    | Open Access

    Aneuploidy (abnormal chromosome number) can enable rapid adaptation to stress conditions, but it also entails fitness costs from gene imbalance. Here, the authors experimentally evolve yeast while forcing maintenance of aneuploidy to identify the mechanisms that promote tolerance of aneuploidy.

    • Alaattin Kaya
    • , Marco Mariotti
    •  & Vadim N. Gladyshev

  • Article
    | Open Access

    Here, the authors report that exhausted HCV-specific CD8+ T cells are marked by upregulation of p53 signaling already detectable in an early phase of chronic HCV infection and by a later development of a repressive chromatin state, and show that chemical targeting of these pathways improves CD8+ T cell metabolism and antiviral function.

    • Valeria Barili
    • , Paola Fisicaro
    •  & Carlo Ferrari

  • Article
    | Open Access

    Histone mimicry of viral components is a strategy to subvert host factors for virus replication. Here, the authors show that an acetylated histone-like motif of the small Hepatitis Delta Antigen (S-HDAg) interacts with the chromatin remodeler BAZ2B to recruit the DNA-dependent RNA polymerase II for HDV RNA replication.

    • Natali Abeywickrama-Samarakoon
    • , Jean-Claude Cortay
    •  & Paul Dény

  • Article
    | Open Access

    Broadly neutralizing antibodies (bNAbs) are being evaluated for HIV post-exposure prophylaxis (PEP) in the setting of vertical transmission. Here, using a macaque model of perinatal SHIV infection, the authors show that PEP for infant macaques within 30–48 h of SHIV exposure is highly effective using either bNAbs or ART.

    • Mariya B. Shapiro
    • , Tracy Cheever
    •  & Nancy L. Haigwood

  • Article
    | Open Access

    Uterine adenomyosis often co-occurs with endometriosis or leiomyoma, but little is known about its molecular underpinnings. Here, the authors show that KRAS mutations are frequent in this disease, which might reduce sensitivity to progestin treatment via epigenetic silencing of the progesterone receptor.

    • Satoshi Inoue
    • , Yasushi Hirota
    •  & Hiroyuki Mano

  • Article
    | Open Access

    The Chlamydia pneumoniae adhesin LIPP plays a role in host cell entry and infection. Here, the authors find that LIPP binds to the host plasma membrane and mediates phosphatidylserine translocation, enhancing pathogen internalization without induction of apoptosis.

    • Jan N. Galle
    • , Tim Fechtner
    •  & Johannes H. Hegemann

  • Article
    | Open Access

    Adolescent idiopathic scoliosis (AIS) is a common pediatric disease leading to spinal deformities. Here, the authors report GWAS followed by genome-wide meta-analysis in up to 79,211 Japanese individuals, identifying 20 genetic loci for AIS, 14 of which were previously unreported, and perform in vitro validation for rs1978060.

    • Ikuyo Kou
    • , Nao Otomo
    •  & Shiro Ikegawa

  • Article
    | Open Access

    Salmonella Typhi produces the typhoid toxin. Here, Fowler et al. show that S. Typhi produces two forms of typhoid toxin that are differentially regulated and display different trafficking properties and different effects when administered to laboratory animals.

    • Casey C. Fowler
    • , Gabrielle Stack
    •  & Jorge E. Galán

  • Article
    | Open Access

    Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

    • Benjamin M. Tang
    • , Maryam Shojaei
    •  & Klaus Schughart

  • Article
    | Open Access

    Here, Bachmann et al. provide data on long-term dynamics of the HIV-1 reservoir in 1,057 individuals on suppressive antiretroviral therapy and show that in 26.6% of individuals the reservoir increases. Viral blips and low-level viremia are significantly associated with a slower reservoir decay.

    • Nadine Bachmann
    • , Chantal von Siebenthal
    •  & Sabine Yerly

  • Article
    | Open Access

    Streptococcus pneumoniae is a common coloniser of the human nasopharynx, but it also causes severe diseases. Here, Weight et al. use an experimental human pneumococcal carriage model to show that bacterial colonisation is associated with invasion of the epithelium and enhancement of immune responses.

    • Caroline M. Weight
    • , Cristina Venturini
    •  & Robert S. Heyderman

  • Article
    | Open Access

    Trehalose metabolism has been linked to Mycobacterium tuberculosis (Mtb) virulence and biofilm formation. Here, using a model of drug-tolerant persisters and metabolomics, the authors dissect the role of trehalose metabolism in Mtb persister formation, linking trehalose-catalytic shift to antibiotic resistance.

    • Jae Jin Lee
    • , Sun-Kyung Lee
    •  & Hyungjin Eoh

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