Pathogenesis articles within Nature Communications

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  • Article
    | Open Access

    Human antigen R (HuR) is a RNA-binding protein. Here the authors investigate its role in adipose tissue and find that it protects mice from diet-induced obesity, prevents adipocyte hypertrophy, and promotes lipolysis, which may at least in part be due to HuR-dependent ATGL mRNA stability regulation demonstrated in-vitro.

    • Jingyuan Li
    • , Li Gong
    •  & Wencheng Zhang

  • Article
    | Open Access

    Respiratory syncytial virus (RSV) can trigger secondary airway bacterial infections. Here, by proteomics and metagenomics analyses of samples from Kenyan children, the authors report that RSV associates with Streptococcus burden and a local upper airway response with direct antibacterial properties.

    • Charles J. Sande
    • , James M. Njunge
    •  & Andrew J. Pollard

  • Article
    | Open Access

    Although Capicua (Cic), a transcriptional repressor, is linked to cancer, little is known about its function in the non-diseased brain. Here, authors show that Cic is strongly expressed in astrocytic and neuronal lineage cells during development and regulates proliferation and lineage selection via de-repression of Ets transcription factors.

    • Shiekh Tanveer Ahmad
    • , Alexandra D. Rogers
    •  & Jennifer A. Chan

  • Article
    | Open Access

    Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.

    • Victoria Cotero
    • , Ying Fan
    •  & Christopher Puleo

  • Article
    | Open Access

    Modulation of the cholinergic pathway and spleen function can reduce inflammation with invasive implants. Here, the authors show that non-invasive ultrasound stimulation of the spleen reduces disease severity in a mouse model of inflammatory arthritis, partly via altering B and T cell function.

    • Daniel P. Zachs
    • , Sarah J. Offutt
    •  & Hubert H. Lim

  • Article
    | Open Access

    Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.

    • Natasja Wulff Pedersen
    • , Anja Holm
    •  & Birgitte Rahbek Kornum

  • Article
    | Open Access

    Phospholipase C β (PLCβ) exhibits immuno-modulatory functions but its role in antiviral innate responses is unclear. Here, the authors provide evidence that PLCβ2 down regulates enterovirus-induced pro-inflammatory responses via inhibition of TAK1 activation, and suggest PLC as a potential therapeutic target.

    • Lin Wang
    • , Yilong Zhou
    •  & Baoxue Ge

  • Article
    | Open Access

    The antibody response during infection with dengue virus is a key component involved in the pathogenesis during secondary infection. Here the authors show antibodies targeting NS1 and the epitopes targeted can be associated with disease severity during human infection.

    • Deshni Jayathilaka
    • , Laksiri Gomes
    •  & Gathsaurie Neelika Malavige

  • Article
    | Open Access

    Salmonella employ a range of strategies to counter host defences during infection. Here, Aulicino et al. use single-cell RNA-sequencing to examine the effects of invasive and non-invasive strains of Salmonella, revealing discrete and divergent immune evasion strategies in infected and bystander dendritic cells.

    • Anna Aulicino
    • , Kevin C. Rue-Albrecht
    •  & Alison Simmons

  • Article
    | Open Access

    Pro-inflammatory factors implicated for the onset of arthritis often have systematic effects, yet arthritis symptoms are mostly limited to the joints. Here the authors show that mechanical strain at the joints promotes the recruitment of monocyte and their differentiation into bone-eroding osteoclast to contribute this tissue specificity.

    • Isabelle Cambré
    • , Djoere Gaublomme
    •  & Dirk Elewaut

  • Article
    | Open Access

    Listeria monocytogenes causes meningitis in newborns. Here, Pägelow et al. present a mouse model of neonatal cerebral listeriosis, and show that nasal inoculation, but not intragastric administration, leads to early brain infection in the absence of bacteraemia during the neonatal period.

    • Dennis Pägelow
    • , Chintan Chhatbar
    •  & Marcus Fulde

  • Article
    | Open Access

    Chr3q26 rearrangements cause overexpression of EVI1 and associate with myeloid neoplasms, but the mechanism behind this association is unclear. Here, using a novel mouse model they show that EVI1 causes premalignant myeloid expansion with suppression of other lineages through upregulation of Spi1/PU.1.

    • Edward Ayoub
    • , Michael P. Wilson
    •  & Archibald S. Perkins

  • Article
    | Open Access

    Streptococcus pneumoniae evades the action of the complement system by expressing an immuno-protective polysaccharide capsule as well as Factor H-binding proteins. Here, Pathak et al. show that these two defence mechanisms are functionally and spatially coordinated on the bacterial cell surface.

    • Anuj Pathak
    • , Jan Bergstrand
    •  & Birgitta Henriques-Normark

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.

    • Angeliki M. Andrianaki
    • , Irene Kyrmizi
    •  & Georgios Chamilos

  • Article
    | Open Access

    The majority of skeletal dysplasia are caused by pathogenic variants in genes required for glycosaminoglycan (GAG) metabolism. Here, Dubail et al. identify genetic variants in the solute carrier family protein SLC10A7 in families with skeletal dysplasia and amelogenesis imperfecta that disrupt GAG synthesis.

    • Johanne Dubail
    • , Céline Huber
    •  & Valérie Cormier-Daire

  • Article
    | Open Access

    NOD2 has been shown to be crucial for immune recognition of Aspergillus infection. Here the authors show that a common NOD2 genetic variant associated with Crohn’s disease is associated with reduced risk of disease due to enhanced antifungal activates of monocytes and macrophages.

    • Mark S. Gresnigt
    • , Cristina Cunha
    •  & Frank L. van de Veerdonk

  • Article
    | Open Access

    Sepsis is a life-threatening condition. Here, the authors show that intermedin alleviates organ injury and decreases mortality in septic mice by concurrently alleviating vascular leakage and inflammatory responses. Patients with high intermedin levels exhibit a low risk of shock, lower severity scores, and greatly improved survival outcomes.

    • Fei Xiao
    • , Denian Wang
    •  & Wei Zhang

  • Article
    | Open Access

    Intron retention (IR) can increase protein diversity and function, and yet unregulated IR may be detrimental to cellular health. This study shows that aberrant IR occurs in ALS and finds nuclear loss of an RNA-binding protein called SFPQ as a new molecular hallmark in this devastating condition.

    • Raphaelle Luisier
    • , Giulia E. Tyzack
    •  & Rickie Patani

  • Article
    | Open Access

    In contrast to HIV, simian immunodeficiency viruses (SIV) do not cause disease in their hosts, and the reasons for this are unclear. Here, Joas et al. incorporate two putative HIV virulence factors into SIV and study effects in infected monkeys, suggesting that species-specific host factors are responsible for HIV pathogenesis.

    • Simone Joas
    • , Erica H. Parrish
    •  & Frank Kirchhoff

  • Article
    | Open Access

    XLP-2 syndrome is caused by XIAP mutation. Here the authors show that mouse and human XIAP-deficient regulatory T cells have defective suppressive function as a result of conversion to proinflammatory cytokine producing cells, an effect that can be prevented by blocking the IL-6 receptor.

    • Wan-Chen Hsieh
    • , Tzu-Sheng Hsu
    •  & Ming-Zong Lai

  • Article
    | Open Access

    During obesity, chronic inflammation leads to insulin resistance and diabetes. Here, Brenachot et al. show that Protein Tyrosine Phosphatase Receptor Gamma is upregulated in obesity by inflammatory signals and correlates with insulin resistance in humans. Its deletion in mouse models of obesity and inflammation ameliorates insulin resistance by suppressing glucose production.

    • Xavier Brenachot
    • , Giorgio Ramadori
    •  & Roberto Coppari

  • Article
    | Open Access

    ROCK is associated with T cell movement in lymph nodes. Here the authors use an LPS lung damage model and two-photon imaging to show that CD8+ T cells in lung tissue engage in ROCK-dependent fast linear migration alternating with bursts of slower confined migration that together optimize contact with target cells.

    • Paulus Mrass
    • , Sreenivasa Rao Oruganti
    •  & Judy L. Cannon

  • Article
    | Open Access

    Deep penetrating nevi (DPN) are unusual melanocytic neoplasms with unknown genetic drivers. Here the authors show that majority of DPN harbor activating mutations in the β-catenin and the MAP-kinase pathways; this characteristic can help in the classification and grading of these distinctive neoplasms.

    • Iwei Yeh
    • , Ursula E. Lang
    •  & Arnaud de la Fouchardière

  • Article
    | Open Access

    Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.

    • Eunice E. To
    • , Ross Vlahos
    •  & Stavros Selemidis

  • Article
    | Open Access

    LOXL1 is a genetic risk factor for pseudoexfoliation syndrome of the eye but a causal variant has not been identified. Here, Pasutto et al., find intronic LOXL1 risk variants influence transcription factor binding and alternative splicing of LOXL1 in affected tissues reducing levels of LOXL1mRNA.

    • Francesca Pasutto
    • , Matthias Zenkel
    •  & Ursula Schlötzer-Schrehardt

  • Article
    | Open Access

    Osteoarthritis (OA) is a debilitating and destructive joint disease for which disease modifying drugs are not available. Here the authors show that extracellular adenosine signalling via the A2AR receptor on chondrocytes is needed to prevent OA and that liposome-bound adenosine injection can treat the pathology in rats.

    • Carmen Corciulo
    • , Matin Lendhey
    •  & Bruce N. Cronstein

  • Article
    | Open Access

    Primary dysmenorrhoea, the most common gynaecologic complaint, remains genetically and pathophysiologically elusive. Here, Li and colleagues identify common variants inZMIZ1 and near NGFconferring risk for primary dysmenorrhoea using genome-wide association study in a Chinese population.

    • Zhiqiang Li
    • , Jianhua Chen
    •  & Yongyong Shi

  • Article
    | Open Access

    Secondary lymphedema is a debilitating disease with no cure. Here the authors show that topical application of an FDA-approved anti-T cell drug tacrolimus potently prevents development and alleviates pathologic changes of established lymphedema in mice, suggesting a new treatment for human patients.

    • Jason C. Gardenier
    • , Raghu P. Kataru
    •  & Babak J. Mehrara

  • Article
    | Open Access

    Shotgun DNA sequencing experiments for microbial genomic analysis are often impractical due to minimum sample input requirements. Here the authors develop a microfluidic sample preparation platform that reduces sample input requirements 100-fold and enables high throughput sequencing from low numbers of cells.

    • Soohong Kim
    • , Joachim De Jonghe
    •  & Paul C. Blainey

  • Article
    | Open Access

    C-reactive protein is a pentameric protein secreted by the liver in response to injury and infection. Here Braiget al. show that conformational changes in CRP on the surface of monocyte-derived microvesicles enable binding of complement C1q and lead to activation of the complement cascade and aggravation of inflammation.

    • David Braig
    • , Tracy L. Nero
    •  & Steffen U. Eisenhardt

  • Article
    | Open Access

    Reduced BMP receptor II signalling underlies pulmonary arterial hypertension (PAH). Here, Hurstet al. show that TNFα subverts BMP signalling by increasing BMP6 expression and signalling via an alternative BMP receptor, ALK2, in pulmonary artery smooth muscle cells to drive abnormal proliferation and PAH.

    • Liam A. Hurst
    • , Benjamin J. Dunmore
    •  & Nicholas W. Morrell

  • Article
    | Open Access

    Non-resolving bacterial pneumonia results in lung tissue damage owing to overactive inflammation. Here the authors show that the mitochondrial DAMP cardiolipin contributes to persistent inflammation by SUMOylating PPARγ, which promotes binding of the corepressor NCOR/HDAC3 complex to the IL-10 promoter.

    • Krishnendu Chakraborty
    • , Mahesh Raundhal
    •  & Prabir Ray

  • Article
    | Open Access

    Crohn’s disease is associated with altered intestinal microbiota. Here, the authors show that the microbe Atopobium parvulumis associated with Crohn’s disease patients, triggers colitis in a mouse model, and that scavenging microbe-induced hydrogen sulfide improved symptoms in mice.

    • Walid Mottawea
    • , Cheng-Kang Chiang
    •  & Alain Stintzi

  • Article
    | Open Access

    Mycobacteria can adapt to the stress of human infection by entering a dormant state. Here the authors show that hypoxia-induced dormancy in M. bovisBCG involves the reprogramming of tRNA wobble modifications and copy numbers, coupled with biased use of synonymous codons in survival genes.

    • Yok Hian Chionh
    • , Megan McBee
    •  & Peter C. Dedon

  • Article
    | Open Access

    Carriers of haemoglobinopathies are protected from severe malaria, likely due to reduced surface expression of virulence factors. Here, Cyrklaff et al. show that, similar to haemoglobinopathies, a transient oxidative insult affects actin reorganization and mitigates the development of cerebral malaria in mice.

    • Marek Cyrklaff
    • , Sirikamol Srismith
    •  & Michael Lanzer

  • Article
    | Open Access

    Binding of virus, HIV-1, to cellular protein Siglec-1 is important for infection of immune cells. Here the authors show that a natural mutation leading to production of truncated Siglec-1 reduces HIV binding and infectivity transfer in vitro, but does not substantially affect infection or AIDS outcome in patients.

    • Javier Martinez-Picado
    • , Paul J. McLaren
    •  & Amalio Telenti

  • Article
    | Open Access

    Alzheimer’s disease (AD) is pathologically characterized by the accumulation of neuritic plaques and neurofibrillary tangles but it is not known whether the neuritic plaque is necessary to drive the conversion of wild-type tau. Here the authors developed a mouse model in which wild-type tau is converted into pathological tau in a neuritic plaque-dependent manner.

    • Tong Li
    • , Kerstin E. Braunstein
    •  & Philip C. Wong

  • Article
    | Open Access

    Genetically engineered mouse models of cancer are useful in identifying oncogenes and tumour suppressors. Here, the authors use gene expression profiles to generate a catalogue of copy number aberrations in 45 mouse models, and compare mouse and human tumours to identify additional drivers of tumorigenesis.

    • Uri Ben-David
    • , Gavin Ha
    •  & Todd R. Golub

  • Article
    | Open Access

    Epidermal intraepithelial lymphocytes (IEL) produce IL-13, but the physiological role of this cytokine production is not clear. Here the authors show that IEL-production of IL-13 is a vital lymphoid stress surveillance mechanism driving crosstalk with epithelial cells to maintain tissue homeostasis and inhibit chemical carcinogenesis in mice.

    • Tim Dalessandri
    • , Greg Crawford
    •  & Jessica Strid

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