Immunology

  • Article
    | Open Access

    Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

    • David Michalovich
    • , Noelia Rodriguez-Perez
    • , Sylwia Smolinska
    • , Michal Pirozynski
    • , David Mayhew
    • , Sorif Uddin
    • , Stephanie Van Horn
    • , Milena Sokolowska
    • , Can Altunbulakli
    • , Andrzej Eljaszewicz
    • , Benoit Pugin
    • , Weronika Barcik
    • , Magdalena Kurnik-Lucka
    • , Ken A. Saunders
    • , Karen D. Simpson
    • , Peter Schmid-Grendelmeier
    • , Ruth Ferstl
    • , Remo Frei
    • , Noriane Sievi
    • , Malcolm Kohler
    • , Pawel Gajdanowicz
    • , Katrine B. Graversen
    • , Katrine Lindholm Bøgh
    • , Marek Jutel
    • , James R. Brown
    • , Cezmi A. Akdis
    • , Edith M. Hessel
    •  & Liam O’Mahony
  • Article
    | Open Access

    miRNA142-3p and Tet2 are separately known to regulate Treg. Here the authors show that miRNA142-3p targets Tet2 and by this opposes Treg differentiation in autoimmune diabetes.

    • Martin G. Scherm
    • , Isabelle Serr
    • , Adam M. Zahm
    • , Jonathan Schug
    • , Saverio Bellusci
    • , Rossella Manfredini
    • , Victoria K. Salb
    • , Katharina Gerlach
    • , Benno Weigmann
    • , Anette-Gabriele Ziegler
    • , Klaus H. Kaestner
    •  & Carolin Daniel
  • Article
    | Open Access

    Graft versus host disease (GvHD) still hinders allogeneic hematopoietic stem cell transplantation. Here, the authors use metabolomics to analyze two cohorts of paired transplant recipients and donors, identifying significant differences in both host- and microbiota-derived metabolites.

    • David Michonneau
    • , Eleonora Latis
    • , Emmanuel Curis
    • , Laetitia Dubouchet
    • , Sivapriya Ramamoorthy
    • , Brian Ingram
    • , Régis Peffault de Latour
    • , Marie Robin
    • , Flore Sicre de Fontbrune
    • , Sylvie Chevret
    • , Lars Rogge
    •  & Gérard Socié
  • Article
    | Open Access

    A Zika virus vaccine should protect the fetus during pregnancy. Here, using a live-attenuated Zika vaccine, the authors show that a higher neutralizing antibody titer is required to protect from in utero transmission than to protect non-pregnant mice and that a single maternal immunization protects the fetus from infection and disease.

    • Chao Shan
    • , Xuping Xie
    • , Huanle Luo
    • , Antonio E. Muruato
    • , Yang Liu
    • , Maki Wakamiya
    • , Jun-Ho La
    • , Jin Mo Chung
    • , Scott C. Weaver
    • , Tian Wang
    •  & Pei-Yong Shi
  • Article
    | Open Access

    Lactobacillus associates with vaginal protection from HIV-1 infection. Here, the authors show that lactobacilli extracellular vesicles contain bacterial proteins and metabolites that inhibit HIV-1 infection in T cells and in human cervico-vaginal and tonsillar tissues ex vivo via altering viral Env proteins.

    • Rogers A. Ñahui Palomino
    • , Christophe Vanpouille
    • , Luca Laghi
    • , Carola Parolin
    • , Kamran Melikov
    • , Peter Backlund
    • , Beatrice Vitali
    •  & Leonid Margolis
  • Article
    | Open Access

    Innate immune cells can be trained by some stimuli or pathogen exposures to be metabolically and epigenetically altered such that they have different responses to subsequent exposures. Here the authors show that low-dose LPS trained macrophages and BCG-trained macrophages have opposing effects on fibrosis and inflammation in the context of systemic sclerosis.

    • Mohamed Jeljeli
    • , Luiza Gama Coelho Riccio
    • , Ludivine Doridot
    • , Charlotte Chêne
    • , Carole Nicco
    • , Sandrine Chouzenoux
    • , Quentin Deletang
    • , Yannick Allanore
    • , Niloufar Kavian
    •  & Frédéric Batteux
  • Article
    | Open Access

    Ageing is associated with clonal hematopoiesis of indeterminate potential (CHIP), which is linked to increased risks of hematological malignancies. Here the authors uncover an epigenetic mechanism through which mutant p53 drives clonal hematopoiesis through interaction with EZH2.

    • Sisi Chen
    • , Qiang Wang
    • , Hao Yu
    • , Maegan L. Capitano
    • , Sasidhar Vemula
    • , Sarah C. Nabinger
    • , Rui Gao
    • , Chonghua Yao
    • , Michihiro Kobayashi
    • , Zhuangzhuang Geng
    • , Aidan Fahey
    • , Danielle Henley
    • , Stephen Z. Liu
    • , Sergio Barajas
    • , Wenjie Cai
    • , Eric R. Wolf
    • , Baskar Ramdas
    • , Zhigang Cai
    • , Hongyu Gao
    • , Na Luo
    • , Yang Sun
    • , Terrence N. Wong
    • , Daniel C. Link
    • , Yunlong Liu
    • , H. Scott Boswell
    • , Lindsey D. Mayo
    • , Gang Huang
    • , Reuben Kapur
    • , Mervin C. Yoder
    • , Hal E. Broxmeyer
    • , Zhonghua Gao
    •  & Yan Liu
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.

    • Lena Lampe
    • , Marius Jentzsch
    • , Sylwia Kierszniowska
    •  & Elena A. Levashina
  • Article
    | Open Access

    The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

    • Jörn F. Ziegler
    • , Chotima Böttcher
    • , Marilena Letizia
    • , Cansu Yerinde
    • , Hao Wu
    • , Inka Freise
    • , Yasmina Rodriguez-Sillke
    • , Ani K. Stoyanova
    • , Martin E. Kreis
    • , Patrick Asbach
    • , Desiree Kunkel
    • , Josef Priller
    • , Ioannis Anagnostopoulos
    • , Anja A. Kühl
    • , Konstanze Miehle
    • , Michael Stumvoll
    • , Florian Tran
    • , Broder Fredrich
    • , Michael Forster
    • , Andre Franke
    • , Christian Bojarski
    • , Rainer Glauben
    • , Britt-Sabina Löscher
    • , Britta Siegmund
    •  & Carl Weidinger
  • Article
    | Open Access

    Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.

    • Arijit Bhattacharya
    • , Philippe Leprohon
    • , Sophia Bigot
    • , Prasad Kottayil Padmanabhan
    • , Angana Mukherjee
    • , Gaétan Roy
    • , Hélène Gingras
    • , Anais Mestdagh
    • , Barbara Papadopoulou
    •  & Marc Ouellette
  • Article
    | Open Access

    The HLA-A*68:01 allele has been associated with severe influenza disease during the 2009 influenza pandemic. Here, the authors analyze influenza nucleoprotein specific HLA-A*68:01-restricted CD8+ T cells from human donors and show immunodominance of these cells in approximately 35% of HLA-A*68:01-expressing donors.

    • C. E. van de Sandt
    • , E. B. Clemens
    • , E. J. Grant
    • , L. C. Rowntree
    • , S. Sant
    • , H. Halim
    • , J. Crowe
    • , A. C. Cheng
    • , T. C. Kotsimbos
    • , M. Richards
    • , A. Miller
    • , S. Y. C. Tong
    • , J. Rossjohn
    • , T. H. O. Nguyen
    • , S. Gras
    • , W. Chen
    •  & K. Kedzierska
  • Article
    | Open Access

    Relapse, reinfection and recrudescence can all cause recurrent infection after treatment of Plasmodium vivax malaria in endemic areas, but are difficult to distinguish. Here the authors show that they can be differentiated probabilistically and thereby demonstrate the high efficacy of primaquine treatment in preventing relapse.

    • Aimee R. Taylor
    • , James A. Watson
    • , Cindy S. Chu
    • , Kanokpich Puaprasert
    • , Jureeporn Duanguppama
    • , Nicholas P. J. Day
    • , Francois Nosten
    • , Daniel E. Neafsey
    • , Caroline O. Buckee
    • , Mallika Imwong
    •  & Nicholas J. White
  • Article
    | Open Access

    Tobacco use is one of the major risk factors for Head and neck squamous cell carcinoma (HNSCC). Here, the authors report an immune-competent syngeneic mouse model that mimics human tobacco-related HNSCC, and develops tumors in the tongue, and report a high response rate to anti-CTLA-4 therapy.

    • Zhiyong Wang
    • , Victoria H. Wu
    • , Michael M. Allevato
    • , Mara Gilardi
    • , Yudou He
    • , Juan Luis Callejas-Valera
    • , Lynn Vitale-Cross
    • , Daniel Martin
    • , Panomwat Amornphimoltham
    • , James Mcdermott
    • , Bryan S. Yung
    • , Yusuke Goto
    • , Alfredo A. Molinolo
    • , Andrew B. Sharabi
    • , Ezra E. W. Cohen
    • , Qianming Chen
    • , J. Guy Lyons
    • , Ludmil B. Alexandrov
    •  & J. Silvio Gutkind
  • Article
    | Open Access

    Climate affects dynamics of infectious diseases, but the impact on respiratory syncytial virus (RSV) epidemiology isn’t well understood. Here, Baker et al. model the influence of temperature, humidity and rainfall on RSV epidemiology in the USA and Mexico and predict impact of climate change on RSV dynamics.

    • Rachel E. Baker
    • , Ayesha S. Mahmud
    • , Caroline E. Wagner
    • , Wenchang Yang
    • , Virginia E. Pitzer
    • , Cecile Viboud
    • , Gabriel A. Vecchi
    • , C. Jessica E. Metcalf
    •  & Bryan T. Grenfell
  • Article
    | Open Access

    Help from CD4+ T cells is important to induce CD8+ T cell memory responses, but mechanistic insights are lacking. Here, the authors show, by transcriptomics and epigenetics, how CD4+ T cells help program memory CD8+ T cells for help-independent recall by antigens, as well as for innate-like recall responses by IL-12/IL-18 and promoting survival by IL-15.

    • Tomasz Ahrends
    • , Julia Busselaar
    • , Tesa M. Severson
    • , Nikolina Bąbała
    • , Evert de Vries
    • , Astrid Bovens
    • , Lodewyk Wessels
    • , Fred van Leeuwen
    •  & Jannie Borst
  • Article
    | Open Access

    Avian influenza A virus (IAV) strains replicate poorly in mammalian hosts, but mechanisms underlying species restriction are incompletely understood. Here, Bogdanow et al. show that avian and mammalian adapted IAV strains have evolved different RNA structure features for regulation of M segment RNA splicing.

    • Boris Bogdanow
    • , Xi Wang
    • , Katrin Eichelbaum
    • , Anne Sadewasser
    • , Immanuel Husic
    • , Katharina Paki
    • , Matthias Budt
    • , Martha Hergeselle
    • , Barbara Vetter
    • , Jingyi Hou
    • , Wei Chen
    • , Lüder Wiebusch
    • , Irmtraud M. Meyer
    • , Thorsten Wolff
    •  & Matthias Selbach
  • Article
    | Open Access

    Urinary tract infections (UTIs) are associated with changes in the gut microbiome. Here, the authors evaluate the relationship between the gut microbiome and development of UTI in kidney transplant patients and show that uropathogenic gut abundance might represent a risk factor for development of bacteriuria and UTI.

    • Matthew Magruder
    • , Adam N. Sholi
    • , Catherine Gong
    • , Lisa Zhang
    • , Emmanuel Edusei
    • , Jennifer Huang
    • , Shady Albakry
    • , Michael J. Satlin
    • , Lars F. Westblade
    • , Carl Crawford
    • , Darshana M. Dadhania
    • , Michelle Lubetzky
    • , Ying Taur
    • , Eric Littman
    • , Lilan Ling
    • , Philip Burnham
    • , Iwijn De Vlaminck
    • , Eric Pamer
    • , Manikkam Suthanthiran
    •  & John Richard Lee
  • Article
    | Open Access

    In breast cancer, the immune infiltration of the tumour associates with clinical outcome. Here, the authors infer immune context based on gene expression data and identify a new independent subtype linked to pro-tumorigenic immune infiltration.

    • Xavier Tekpli
    • , Tonje Lien
    • , Andreas Hagen Røssevold
    • , Daniel Nebdal
    • , Elin Borgen
    • , Hege Oma Ohnstad
    • , Jon Amund Kyte
    • , Johan Vallon-Christersson
    • , Marie Fongaard
    • , Eldri Undlien Due
    • , Lisa Gregusson Svartdal
    • , My Anh Tu Sveli
    • , Øystein Garred
    • , Anne-Lise Børresen-Dale
    • , Ellen Schlichting
    • , Torill Sauer
    • , Jürgen Geisler
    • , Solveig Hofvind
    • , Tone F. Bathen
    • , Olav Engebråten
    • , Gry Aarum Geitvik
    • , Anita Langerød
    • , Rolf Kåresen
    • , Gunhild Mari Mælandsmo
    • , Ole Christian Lingjærde
    • , Helle Kristine Skjerven
    • , Daehoon Park
    • , Britt Fritzman
    • , Arnoldo Frigessi
    • , Kristine Kleivi Sahlberg
    • , Therese Sørlie
    • , Hege G. Russnes
    • , Bjørn Naume
    •  & Vessela N. Kristensen
  • Article
    | Open Access

    Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

    • Alain Vandormael
    • , Adam Akullian
    • , Mark Siedner
    • , Tulio de Oliveira
    • , Till Bärnighausen
    •  & Frank Tanser
  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    • , Yongge Zhao
    • , Mina O. Seedhom
    • , Christelle Harly
    • , Izumi Ohigashi
    • , Michael Kelly
    • , Yousuke Takahama
    • , Jonathan W. Yewdell
    • , Maggie Cam
    •  & Avinash Bhandoola
  • Article
    | Open Access

    Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.

    • Nhan Huynh
    • , Qiuxiang Ou
    • , Pendleton Cox
    • , Roland Lill
    •  & Kirst King-Jones
  • Article
    | Open Access

    One measurement of tuberculosis vaccine efficacy in clinical trials is prevention of disease, but different mechanisms can underlie disease prevention. Here, the authors develop a mathematical model that allows to identify mechanisms of action of a vaccine preventing TB disease.

    • Mario Tovar
    • , Sergio Arregui
    • , Dessislava Marinova
    • , Carlos Martín
    • , Joaquín Sanz
    •  & Yamir Moreno
  • Article
    | Open Access

    Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.

    • Liangrong Shi
    • , Junjun Wang
    • , Nianhua Ding
    • , Yi Zhang
    • , Yibei Zhu
    • , Shunli Dong
    • , Xiaohui Wang
    • , Changli Peng
    • , Chunhui Zhou
    • , Ledu Zhou
    • , Xiaodong Li
    • , Hongbing Shi
    • , Wei Wu
    • , Xueyin Long
    • , Changping Wu
    •  & Weihua Liao
  • Article
    | Open Access

    Visualisation tools that use dimensionality reduction, such as t-SNE, provide poor visualisation on large data sets of millions of observations. Here the authors present opt-SNE, that automatically finds data set-tailored parameters for t-SNE to optimise visualisation and improve analysis.

    • Anna C. Belkina
    • , Christopher O. Ciccolella
    • , Rina Anno
    • , Richard Halpert
    • , Josef Spidlen
    •  & Jennifer E. Snyder-Cappione
  • Perspective
    | Open Access

    Dendritic cells (DCs) have been explored as a promising strategy for cancer immunotherapy. In this Perspective, the authors discuss the different types of DCs and their therapeutic potential in the context of vaccines for personalized cancer therapy.

    • Caleb R. Perez
    •  & Michele De Palma
  • Article
    | Open Access

    Cytotoxic T lymphocytes (CTLs) eliminate virus-infected and cancerous cells by secreting the pore-forming protein (perforin) and pro-apoptotic serine proteases (granzymes). Here authors show that two mechanisms protect the membranes of CTLs from disruption by perforin and granzymes.

    • Jesse A. Rudd-Schmidt
    • , Adrian W. Hodel
    • , Tahereh Noori
    • , Jamie A. Lopez
    • , Hyun-Jung Cho
    • , Sandra Verschoor
    • , Annette Ciccone
    • , Joseph A. Trapani
    • , Bart W. Hoogenboom
    •  & Ilia Voskoboinik
  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    • , Lars L. P. Hanssen
    • , Jelena M. Telenius
    • , Douglas R. Higgs
    •  & Jim R. Hughes
  • Article
    | Open Access

    Myeloid-derived growth factor (MYDGF) is an angiogenic growth factor with therapeutic potential for ischemic tissue repair and the receptor is still unknown. Here the authors present the crystal structure of human MYDGF and identify its functional epitope through mutagenesis studies.

    • Rebecca Ebenhoch
    • , Abbas Akhdar
    • , Marc R. Reboll
    • , Mortimer Korf-Klingebiel
    • , Priyanka Gupta
    • , Julie Armstrong
    • , Yining Huang
    • , Lee Frego
    • , Irina Rybina
    • , John Miglietta
    • , Anton Pekcec
    • , Kai C. Wollert
    •  & Herbert Nar
  • Article
    | Open Access

    Here, the authors identify a broadly neutralizing antibody from an HIV-infected person that recognizes the membrane-proximal external region (MPER) of HIV envelope glycoprotein (Env) and has a short CDRH3 and low polyreactivity. Structural analysis shows how the antibody binds the MPER and Env on the viral membrane.

    • Lei Zhang
    • , Adriana Irimia
    • , Lingling He
    • , Elise Landais
    • , Kimmo Rantalainen
    • , Daniel P. Leaman
    • , Thomas Vollbrecht
    • , Armando Stano
    • , Daniel I. Sands
    • , Arthur S. Kim
    • , George Miiro
    • , Jennifer Serwanga
    • , Anton Pozniak
    • , Dale McPhee
    • , Oliver Manigart
    • , Lawrence Mwananyanda
    • , Etienne Karita
    • , André Inwoley
    • , Walter Jaoko
    • , Jack DeHovitz
    • , Linda-Gail Bekker
    • , Punnee Pitisuttithum
    • , Robert Paris
    • , Susan Allen
    • , Pascal Poignard
    • , Dennis R. Burton
    • , Ben Murrell
    • , Andrew B. Ward
    • , Jiang Zhu
    • , Ian A. Wilson
    •  & Michael B. Zwick
  • Article
    | Open Access

    ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.

    • Yifeng Zhang
    • , Fabien Thery
    • , Nicholas C. Wu
    • , Emma K. Luhmann
    • , Olivier Dussurget
    • , Mariko Foecke
    • , Clara Bredow
    • , Daniel Jiménez-Fernández
    • , Kevin Leandro
    • , Antje Beling
    • , Klaus-Peter Knobeloch
    • , Francis Impens
    • , Pascale Cossart
    •  & Lilliana Radoshevich
  • Article
    | Open Access

    The restriction of appropriate tumour-specific antigens is a current limitation for T cell-engaging immunotherapy. Here, the authors have designed a new system constituted by two halve antibodies, which engage T cells once binding to two different antigens, to specifically eliminate double positive cells in preclinical leukemia and breast cancer mouse models.

    • Agnes Banaszek
    • , Thomas G. P. Bumm
    • , Boris Nowotny
    • , Maria Geis
    • , Kim Jacob
    • , Matthias Wölfl
    • , Johannes Trebing
    • , Kirstin Kucka
    • , Dina Kouhestani
    • , Tea Gogishvili
    • , Bastian Krenz
    • , Justina Lutz
    • , Leo Rasche
    • , Dirk Hönemann
    • , Hannes Neuweiler
    • , Julia C. Heiby
    • , Ralf C. Bargou
    • , Harald Wajant
    • , Hermann Einsele
    • , Gert Riethmüller
    •  & Gernot Stuhler
  • Article
    | Open Access

    ‘Missing self’ is a mode of natural killer (NK) cell activation aimed to detect the lack of HLA-I molecules on infected or neoplastic cells. Here, the authors show that mismatch between donor HLA-I and cognate receptors on recipient NK cells mediates microvascular inflammation-associated graft rejection, a pathology that is preventable by mTOR inhibition.

    • Alice Koenig
    • , Chien-Chia Chen
    • , Antoine Marçais
    • , Thomas Barba
    • , Virginie Mathias
    • , Antoine Sicard
    • , Maud Rabeyrin
    • , Maud Racapé
    • , Jean-Paul Duong-Van-Huyen
    • , Patrick Bruneval
    • , Alexandre Loupy
    • , Sébastien Dussurgey
    • , Stéphanie Ducreux
    • , Vannary Meas-Yedid
    • , Jean-Christophe Olivo-Marin
    • , Héléna Paidassi
    • , Romain Guillemain
    • , Jean-Luc Taupin
    • , Jasper Callemeyn
    • , Emmanuel Morelon
    • , Antonino Nicoletti
    • , Béatrice Charreau
    • , Valérie Dubois
    • , Maarten Naesens
    • , Thierry Walzer
    • , Thierry Defrance
    •  & Olivier Thaunat
  • Article
    | Open Access

    Skewing of X chromosome inactivation (XCI) occurs when the silencing of one parental X chromosome is non-random. Here, Zito et al. report XCI patterns in lymphoblastoid cell lines, blood, subcutaneous adipose tissue samples and skin samples of monozygotic and dizygotic twins and find XCI skew to associate with tissue and age.

    • Antonino Zito
    • , Matthew N. Davies
    • , Pei-Chien Tsai
    • , Susanna Roberts
    • , Rosa Andres-Ejarque
    • , Stefano Nardone
    • , Jordana T. Bell
    • , Chloe C. Y. Wong
    •  & Kerrin S. Small
  • Article
    | Open Access

    The role of Africa in the global spread of highly pathogenic avian influenza (HPAI) is not well understood. Here, using evolutionary analyses, the authors show that Africa mainly acts as ecological sink for HPAI H5, and reveal varying paths of HPAI incursions either through domestic or wild birds.

    • Alice Fusaro
    • , Bianca Zecchin
    • , Bram Vrancken
    • , Celia Abolnik
    • , Rose Ademun
    • , Abdou Alassane
    • , Abdelsatar Arafa
    • , Joseph Adongo Awuni
    • , Emmanuel Couacy-Hymann
    • , M.’ Bétiégué Coulibaly
    • , Nicolas Gaidet
    • , Emilie Go-Maro
    • , Tony Joannis
    • , Simon Dickmu Jumbo
    • , Germaine Minoungou
    • , Clement Meseko
    • , Maman Moutari Souley
    • , Deo Birungi Ndumu
    • , Ismaila Shittu
    • , Augustin Twabela
    • , Abel Wade
    • , Lidewij Wiersma
    • , Yao P. Akpeli
    • , Gianpiero Zamperin
    • , Adelaide Milani
    • , Philippe Lemey
    •  & Isabella Monne
  • Article
    | Open Access

    Brain damage induces systemic inflammation, but insights and implication of this induction is still unclear. Here the authors show, using rat and mouse focal cerebral ischemia models, that the damaged brain signals via the VEGF-C/VEFGR3 axis to activate inflammatory responses in the draining cervical lymph nodes to induce systemic inflammation.

    • Elga Esposito
    • , Bum Ju Ahn
    • , Jingfei Shi
    • , Yoshihiko Nakamura
    • , Ji Hyun Park
    • , Emiri T. Mandeville
    • , Zhanyang Yu
    • , Su Jing Chan
    • , Rakhi Desai
    • , Ayumi Hayakawa
    • , Xunming Ji
    • , Eng H. Lo
    •  & Kazuhide Hayakawa
  • Article
    | Open Access

    NLRP3 activation by Leishmania parasites is critical to the outcome of the disease. Here the authors show that LRV, a virus infecting Leishmania strains associated with more severe human disease, enables the parasite to suppress the inflammasome by activating type 1 interferon through TLR3, which leads to autophagy-mediated NLRP3 degradation.

    • Renan V. H. de Carvalho
    • , Djalma S. Lima-Junior
    • , Marcus Vinícius G. da Silva
    • , Marisa Dilucca
    • , Tamara S. Rodrigues
    • , Catarina V. Horta
    • , Alexandre L. N. Silva
    • , Patrick F. da Silva
    • , Fabiani G. Frantz
    • , Lucas B. Lorenzon
    • , Marcos Michel Souza
    • , Fausto Almeida
    • , Lilian M. Cantanhêde
    • , Ricardo de Godoi M. Ferreira
    • , Angela K. Cruz
    •  & Dario S. Zamboni
  • Article
    | Open Access

    Cellular overgrowth and fibrosis in the foreign body response can compromise the function of transplanted cells. Here, the authors report on the zwitterionically modified alginates for the encapsulation of cells to reduce cellular overgrowth and demonstrate application in mice, dogs and pigs.

    • Qingsheng Liu
    • , Alan Chiu
    • , Long-Hai Wang
    • , Duo An
    • , Monica Zhong
    • , Alexandra M. Smink
    • , Bart J. de Haan
    • , Paul de Vos
    • , Kevin Keane
    • , Andreas Vegge
    • , Esther Y. Chen
    • , Wei Song
    • , Wendy F. Liu
    • , James Flanders
    • , Claude Rescan
    • , Lars Groth Grunnet
    • , Xi Wang
    •  & Minglin Ma
  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    • , Shu-Chen Hung
    • , Weiqi Wang
    • , Shin-Heng Chiou
    • , Claudia Macaubas
    • , Birgitte Kornum
    • , Lu Tian
    • , Huang Huang
    • , Lital Adler
    • , Grant Weaver
    • , Liying Lu
    • , Alexandra Ilstad-Minnihan
    • , Sriram Somasundaram
    • , Sashi Ayyangar
    • , Mark M. Davis
    • , Lawrence J. Stern
    •  & Elizabeth D. Mellins
  • Article
    | Open Access

    Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy.

    • Catarina F. Almeida
    • , Srinivasan Sundararaj
    • , Jérôme Le Nours
    • , T. Praveena
    • , Benjamin Cao
    • , Satvika Burugupalli
    • , Dylan G. M. Smith
    • , Onisha Patel
    • , Manfred Brigl
    • , Daniel G. Pellicci
    • , Spencer J. Williams
    • , Adam P. Uldrich
    • , Dale I. Godfrey
    •  & Jamie Rossjohn
  • Article
    | Open Access

    Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

    • Lenine J. P. Liebenberg
    • , Lyle R. McKinnon
    • , Nonhlanhla Yende-Zuma
    • , Nigel Garrett
    • , Cheryl Baxter
    • , Ayesha B. M. Kharsany
    • , Derseree Archary
    • , Anne Rositch
    • , Natasha Samsunder
    • , Leila E. Mansoor
    • , Jo-Ann S. Passmore
    • , Salim S. Abdool Karim
    •  & Quarraisha Abdool Karim
  • Article
    | Open Access

    Treatment with demethylation agents can reactivate transposable elements. Here in glioblastoma, the authors also show that this is accompanied by de novo presentation of TE-derived peptides on MHC class I molecules.

    • Yu Kong
    • , Christopher M. Rose
    • , Ashley A. Cass
    • , Alexander G. Williams
    • , Martine Darwish
    • , Steve Lianoglou
    • , Peter M. Haverty
    • , Ann-Jay Tong
    • , Craig Blanchette
    • , Matthew L. Albert
    • , Ira Mellman
    • , Richard Bourgon
    • , John Greally
    • , Suchit Jhunjhunwala
    •  & Haiyin Chen-Harris
  • Article
    | Open Access

    Multiplexed genome engineering with Cas9 can increase efficiency but also the risk of unintended alterations. Here the authors demonstrate the use of multiplexed base editors on primary T cells with reduced translocation frequency.

    • Beau R. Webber
    • , Cara-lin Lonetree
    • , Mitchell G. Kluesner
    • , Matthew J. Johnson
    • , Emily J. Pomeroy
    • , Miechaleen D. Diers
    • , Walker S. Lahr
    • , Garrett M. Draper
    • , Nicholas J. Slipek
    • , Branden A. Smeester
    • , Klaus N. Lovendahl
    • , Amber N. McElroy
    • , Wendy R. Gordon
    • , Mark J. Osborn
    •  & Branden S. Moriarity
  • Article
    | Open Access

    Metabolic syndrome is characterized by complex phenotypes that increases the risk of cardiovascular disease and type 2 diabetes. Here the authors’ integrative network analysis suggests BTK inhibitor ibrutinib to be a promising treatment through its obesity-associated inflammation lowering effect.

    • Karla Misselbeck
    • , Silvia Parolo
    • , Francesca Lorenzini
    • , Valeria Savoca
    • , Lorena Leonardelli
    • , Pranami Bora
    • , Melissa J. Morine
    • , Maria Caterina Mione
    • , Enrico Domenici
    •  & Corrado Priami
  • Article
    | Open Access

    There is limited knowledge of markers to identify various waves of murine embryonic hematopoiesis. Here, the authors show that the expression of toll-like receptor 2 (TLR2) on E7.5 c-kit+ cells marks the emergence of erythro-myeloid progenitor precursors and that the Tlr2 locus is active in E8.5 precursors of adult HSCs.

    • Jana Balounová
    • , Iva Šplíchalová
    • , Martina Dobešová
    • , Michal Kolář
    • , Karel Fišer
    • , Jan Procházka
    • , Radislav Sedlacek
    • , Andrea Jurisicova
    • , Hoon-ki Sung
    • , Vladimír Kořínek
    • , Meritxell Alberich-Jorda
    • , Isabelle Godin
    •  & Dominik Filipp
  • Article
    | Open Access

    Inflammatory responses must be induced and resolved timely to serve protection from pathogens without inducing excessive tissue damage. Here the authors use live imaging in zebrafish to show that the intracellular trafficking of two chemokine receptors, Cxcr1 and Cxcr2, is differentially regulated on activated neutrophils to control their clustering and dispersal, respectively.

    • Caroline Coombs
    • , Antonios Georgantzoglou
    • , Hazel A. Walker
    • , Julian Patt
    • , Nicole Merten
    • , Hugo Poplimont
    • , Elisabeth M. Busch-Nentwich
    • , Sarah Williams
    • , Christina Kotsi
    • , Evi Kostenis
    •  & Milka Sarris
  • Article
    | Open Access

    LncRNA loci potentially contain multiple modes that can exert function, including DNA regulatory elements. Here, the authors generated genetic models in mice to dissect the role of the syntenically conserved lncRNA Firre in the context of hematopoiesis.

    • Jordan P. Lewandowski
    • , James C. Lee
    • , Taeyoung Hwang
    • , Hongjae Sunwoo
    • , Jill M. Goldstein
    • , Abigail F. Groff
    • , Nydia P. Chang
    • , William Mallard
    • , Adam Williams
    • , Jorge Henao-Meija
    • , Richard A. Flavell
    • , Jeannie T. Lee
    • , Chiara Gerhardinger
    • , Amy J. Wagers
    •  & John L. Rinn
  • Article
    | Open Access

    Engineered T cells work as living therapeutics, but are prone to hyperreactivity and exhaustion. Here the authors improve CAR T cell antitumor responses by simultaneously targeting a CAR to TCR locus and IL-12 to PD1 locus, placing the transgenes under a naturally regulated transcriptional network while disrupting unwanted signals.

    • Mohit Sachdeva
    • , Brian W. Busser
    • , Sonal Temburni
    • , Billal Jahangiri
    • , Anne-Sophie Gautron
    • , Alan Maréchal
    • , Alexandre Juillerat
    • , Alan Williams
    • , Stéphane Depil
    • , Philippe Duchateau
    • , Laurent Poirot
    •  & Julien Valton
  • Article
    | Open Access

    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

    • Paul A Lyons
    • , James E Peters
    • , Federico Alberici
    • , James Liley
    • , Richard M. R. Coulson
    • , William Astle
    • , Chiara Baldini
    • , Francesco Bonatti
    • , Maria C Cid
    • , Heather Elding
    • , Giacomo Emmi
    • , Jörg Epplen
    • , Loïc Guillevin
    • , David R. W. Jayne
    • , Tao Jiang
    • , Iva Gunnarsson
    • , Peter Lamprecht
    • , Stephen Leslie
    • , Mark A. Little
    • , Davide Martorana
    • , Frank Moosig
    • , Thomas Neumann
    • , Sophie Ohlsson
    • , Stefanie Quickert
    • , Giuseppe A. Ramirez
    • , Barbara Rewerska
    • , Georg Schett
    • , Renato A. Sinico
    • , Wojciech Szczeklik
    • , Vladimir Tesar
    • , Damjan Vukcevic
    • , Mohammed Akil
    • , Jonathan Barratt
    • , Neil Basu
    • , Adam S. Butterworth
    • , Ian Bruce
    • , Michael Clarkson
    • , Niall Conlon
    • , Bhaskar DasGupta
    • , Timothy W. R. Doulton
    • , Georgina Espígol-Frigolé
    • , Oliver Flossmann
    • , Armando Gabrielli
    • , Jolanta Gasior
    • , Gina Gregorini
    • , Giuseppe Guida
    • , José Hernández-Rodríguez
    • , Zdenka Hruskova
    • , Amy Hudson
    • , Ann Knight
    • , Peter Lanyon
    • , Raashid Luqmani
    • , Malgorzata Magliano
    • , Angelo A. Manfredi
    • , Christopher Marguerie
    • , Federica Maritati
    • , Chiara Marvisi
    • , Neil J. McHugh
    • , Eamonn Molloy
    • , Allan Motyer
    • , Chetan Mukhtyar
    • , Leonid Padyukov
    • , Alberto Pesci
    • , Sergio Prieto-Gonzalez
    • , Marc Ramentol-Sintas
    • , Petra Reis
    • , Dario Roccatello
    • , Patrizia Rovere-Querini
    • , Carlo Salvarani
    • , Francesca Santarsia
    • , Roser Solans-Laque
    • , Nicole Soranzo
    • , Jo Taylor
    • , Julie Wessels
    • , Jochen Zwerina
    • , Benjamin Terrier
    • , Richard A Watts
    • , Augusto Vaglio
    • , Julia U Holle
    • , Chris Wallace
    •  & Kenneth G. C. Smith