Pathogenesis

  • Article
    | Open Access

    Fibroblast contributions to lung fibrosis and in particular their crosstalk with immune cells in the lung are incompletely understood. Here, the authors show an overall immune suppressive environment transcriptionally controlled and maintained by fibroblasts in lung fibrosis with possible therapeutic implications.

    • Lu Cui
    • , Shih-Yu Chen
    • , Tristan Lerbs
    • , Jin-Wook Lee
    • , Pablo Domizi
    • , Sydney Gordon
    • , Yong-hun Kim
    • , Garry Nolan
    • , Paola Betancur
    •  & Gerlinde Wernig
  • 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
    • , Xu Shi
    • , Xi Chen
    • , Yu Yu
    • , Zheng-Cheng Yu
    • , Tsutomu Miyamoto
    • , Meng-Horng Lee
    • , Vivek Singh
    • , Ryoichi Asaka
    • , Geoffrey Shimberg
    • , Michele I. Vitolo
    • , Stuart S. Martin
    • , Denis Wirtz
    • , Ronny Drapkin
    • , Jianhua Xuan
    • , Tian-Li Wang
    •  & 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
    • , Hoang Van Phan
    • , Jing Lin
    • , Bharathi Laxman
    • , Steven R. White
    • , Philip A. Verhoef
    • , Gökhan M. Mutlu
    • , Bhakti Patel
    •  & Savaş Tay
  • Article
    | Open Access

    Some strains of Mycobacterium tuberculosis seem to be able to avoid host defense systems. Here the authors stratify patients by severity of tuberculosis and find correlations with the level of IL-1β production by macrophages exposed to these isolates.

    • Jeremy Sousa
    • , Baltazar Cá
    • , Ana Raquel Maceiras
    • , Luisa Simões-Costa
    • , Kaori L. Fonseca
    • , Ana Isabel Fernandes
    • , Angélica Ramos
    • , Teresa Carvalho
    • , Leandro Barros
    • , Carlos Magalhães
    • , Álvaro Chiner-Oms
    • , Henrique Machado
    • , Maria Isabel Veiga
    • , Albel Singh
    • , Rui Pereira
    • , António Amorim
    • , Jorge Vieira
    • , Cristina P. Vieira
    • , Apoorva Bhatt
    • , Fernando Rodrigues
    • , Pedro N. S. Rodrigues
    • , Sebastien Gagneux
    • , António Gil Castro
    • , João Tiago Guimarães
    • , Helder Novais Bastos
    • , Nuno S. Osório
    • , Iñaki Comas
    •  & Margarida Saraiva
  • 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
    • , Murielle Baltazar
    • , Madikay Senghore
    • , Shadia Khandaker
    • , Rong Xu
    • , Laura Bricio-Moreno
    • , Marie Yang
    • , Christopher G. Dowson
    • , Dean B. Everett
    • , Daniel R. Neill
    •  & 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
    • , Felipe da Veiga Leprevost
    • , Shilpa R. Tekula
    • , Hui-Yin Chang
    • , Marissa J. White
    • , Ashley Cimino-Mathews
    • , Boris Burman
    • , Venkatesha Basrur
    • , Pedram Argani
    • , Alexey I. Nesvizhskii
    •  & Celina G. Kleer
  • Article
    | Open Access

    Organoid technology has enabled the generation of several breast cancer organoids. Here, the authors combine propagation of normal human mammary tissues with mass cytometry to evaluate the ability of organoid culture technologies to preserve stem cells and differentiated cell types.

    • Jennifer M. Rosenbluth
    • , Ron C. J. Schackmann
    • , G. Kenneth Gray
    • , Laura M. Selfors
    • , Carman Man-Chung Li
    • , Mackenzie Boedicker
    • , Hendrik J. Kuiken
    • , Andrea Richardson
    • , Jane Brock
    • , Judy Garber
    • , Deborah Dillon
    • , Norman Sachs
    • , Hans Clevers
    •  & Joan S. Brugge
  • 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
    • , Simone McInerny
    • , James A. Morgan
    • , Simone M. Rowley
    • , Jue Er Amanda Lee
    • , Na Li
    • , Kylie L. Gorringe
    • , Paul A. James
    •  & Ian G. Campbell
  • Article
    | Open Access

    Expression of Cas9 and gRNA from viral vectors in vivo may cause off-target activity. Here the authors present NanoMEDIC, which uses nanovesicles to transiently deliver editing machinery to hard-to-transfect cells.

    • Peter Gee
    • , Mandy S. Y. Lung
    • , Yuya Okuzaki
    • , Noriko Sasakawa
    • , Takahiro Iguchi
    • , Yukimasa Makita
    • , Hiroyuki Hozumi
    • , Yasutomo Miura
    • , Lucy F. Yang
    • , Mio Iwasaki
    • , Xiou H. Wang
    • , Matthew A. Waller
    • , Nanako Shirai
    • , Yasuko O. Abe
    • , Yoko Fujita
    • , Kei Watanabe
    • , Akihiro Kagita
    • , Kumiko A. Iwabuchi
    • , Masahiko Yasuda
    • , Huaigeng Xu
    • , Takeshi Noda
    • , Jun Komano
    • , Hidetoshi Sakurai
    • , Naoto Inukai
    •  & Akitsu Hotta
  • 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
    • , Julia Volz
    • , Michael Koeppen
    • , Harald F. Langer
    • , Georg Hansmann
    • , Ekaterina Legchenko
    • , Tobias Geisler
    • , Tamam Bakchoul
    • , Claudia Eggstein
    • , Helene A. Häberle
    • , Bernhard Nieswandt
    •  & 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
    • , Qionghua Zhu
    • , Liang Fang
    • , Haiyue Liu
    • , Hazel Quinn
    • , Marlon Stoeckius
    • , Christine Kocks
    • , Walter Birchmeier
    •  & Nikolaus Rajewsky
  • Article
    | Open Access

    STEAP4 promotes the uptake of copper, and copper is known to be enhanced in cancer tissues. Here, the authors show that STEAP4 is induced by IL17, which is increased in inflamed tissues, consequently the increased copper levels activate NFκB signalling and suppression of apoptosis.

    • Yun Liao
    • , Junjie Zhao
    • , Katarzyna Bulek
    • , Fangqiang Tang
    • , Xing Chen
    • , Gang Cai
    • , Shang Jia
    • , Paul L. Fox
    • , Emina Huang
    • , Theresa T. Pizarro
    • , Matthew F. Kalady
    • , Mark W. Jackson
    • , Shideng Bao
    • , Ganes C. Sen
    • , George R. Stark
    • , Christopher J. Chang
    •  & Xiaoxia Li
  • 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
    • , Stephen A. Murray
    • , Mary E. Dickinson
    • , Maja Bucan
    • , Lauryl M. J. Nutter
    • , Kevin A. Peterson
    • , Hamed Haselimashhadi
    • , Ann M. Flenniken
    • , Hugh Morgan
    • , Henrik Westerberg
    • , Tomasz Konopka
    • , Chih-Wei Hsu
    • , Audrey Christiansen
    • , Denise G. Lanza
    • , Arthur L. Beaudet
    • , Jason D. Heaney
    • , Helmut Fuchs
    • , Valerie Gailus-Durner
    • , Tania Sorg
    • , Jan Prochazka
    • , Vendula Novosadova
    • , Christopher J. Lelliott
    • , Hannah Wardle-Jones
    • , Sara Wells
    • , Lydia Teboul
    • , Heather Cater
    • , Michelle Stewart
    • , Tertius Hough
    • , Wolfgang Wurst
    • , Radislav Sedlacek
    • , David J. Adams
    • , John R. Seavitt
    • , Glauco Tocchini-Valentini
    • , Fabio Mammano
    • , Robert E. Braun
    • , Colin McKerlie
    • , Yann Herault
    • , Martin Hrabě de Angelis
    • , Ann-Marie Mallon
    • , K. C.  Kent Lloyd
    • , Steve D. M. Brown
    • , Helen Parkinson
    • , Terrence F. Meehan
    • , Damian Smedley
    • , J. C. Ambrose
    • , P. Arumugam
    • , E. L. Baple
    • , M. Bleda
    • , F. Boardman-Pretty
    • , J. M. Boissiere
    • , C. R. Boustred
    • , H. Brittain
    • , M. J. Caulfield
    • , G. C. Chan
    • , C. E. H. Craig
    • , L. C. Daugherty
    • , A. de Burca
    • , A. Devereau
    • , G. Elgar
    • , R. E. Foulger
    • , T. Fowler
    • , P. Furió-Tarí
    • , J. M. Hackett
    • , D. Halai
    • , A. Hamblin
    • , S. Henderson
    • , J. E. Holman
    • , T. J. P. Hubbard
    • , K. Ibáñez
    • , R. Jackson
    • , L. J. Jones
    • , D. Kasperaviciute
    • , M. Kayikci
    • , L. Lahnstein
    • , K. Lawson
    • , S. E. A. Leigh
    • , I. U. S. Leong
    • , F. J. Lopez
    • , F. Maleady-Crowe
    • , J. Mason
    • , E. M. McDonagh
    • , L. Moutsianas
    • , M. Mueller
    • , N. Murugaesu
    • , A. C. Need
    • , C. A. Odhams
    • , C. Patch
    • , D. Perez-Gil
    • , D. Polychronopoulos
    • , J. Pullinger
    • , T. Rahim
    • , A. Rendon
    • , P. Riesgo-Ferreiro
    • , T. Rogers
    • , M. Ryten
    • , K. Savage
    • , K. Sawant
    • , R. H. Scott
    • , A. Siddiq
    • , A. Sieghart
    • , K. R. Smith
    • , A. Sosinsky
    • , W. Spooner
    • , H. E. Stevens
    • , A. Stuckey
    • , R. Sultana
    • , E. R. A. Thomas
    • , S. R. Thompson
    • , C. Tregidgo
    • , A. Tucci
    • , E. Walsh
    • , S. A. Watters
    • , M. J. Welland
    • , E. Williams
    • , K. Witkowska
    • , S. M. Wood
    • , M. Zarowiecki
    • , Susan Marschall
    • , Christoph Lengger
    • , Holger Maier
    • , Claudia Seisenberger
    • , Antje Bürger
    • , Ralf Kühn
    • , Joel Schick
    • , Andreas Hörlein
    • , Oskar Oritz
    • , Florian Giesert
    • , Joachim Beig
    • , Janet Kenyon
    • , Gemma Codner
    • , Martin Fray
    • , Sara J. Johnson
    • , James Cleak
    • , Zsombor Szoke-Kovacs
    • , David Lafont
    • , Valerie E. Vancollie
    • , Robbie S. B. McLaren
    • , Lena Hughes-Hallett
    • , Christine Rowley
    • , Emma Sanderson
    • , Antonella Galli
    • , Elizabeth Tuck
    • , Angela Green
    • , Catherine Tudor
    • , Emma Siragher
    • , Monika Dabrowska
    • , Cecilia Icoresi Mazzeo
    • , Mark Griffiths
    • , David Gannon
    • , Brendan Doe
    • , Nicola Cockle
    • , Andrea Kirton
    • , Joanna Bottomley
    • , Catherine Ingle
    • , Edward Ryder
    • , Diane Gleeson
    • , Ramiro Ramirez-Solis
    • , Marie-Christine Birling
    • , Guillaume Pavlovic
    • , Abdel Ayadi
    • , Meziane Hamid
    • , Ghina Bou About
    • , Marie-France Champy
    • , Hugues Jacobs
    • , Olivia Wendling
    • , Sophie Leblanc
    • , Laurent Vasseur
    • , Elissa J. Chesler
    • , Vivek Kumar
    • , Jacqueline K. White
    • , Karen L. Svenson
    • , Jean-Paul Wiegand
    • , Laura L. Anderson
    • , Troy Wilcox
    • , James Clark
    • , Jennifer Ryan
    • , James Denegre
    • , Tim Stearns
    • , Vivek Philip
    • , Catherine Witmeyer
    • , Lindsay Bates
    • , Zachary Seavey
    • , Pamela Stanley
    • , Amelia Willet
    • , Willson Roper
    • , Julie Creed
    • , Michayla Moore
    • , Alex Dorr
    • , Pamelia Fraungruber
    • , Rose Presby
    • , Matthew Mckay
    • , Dong Nguyen-Bresinsky
    • , Leslie Goodwin
    • , Rachel Urban
    •  & 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
    • , Alexander Tyshkovskiy
    • , Xuming Zhou
    • , Michelle L. Hulke
    • , Siming Ma
    • , Maxim V. Gerashchenko
    • , Amnon Koren
    •  & 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
    • , Barbara Montanini
    • , Greta Acerbi
    • , Anita Filippi
    • , Giovanna Forleo
    • , Chiara Romualdi
    • , Manuela Ferracin
    • , Francesca Guerrieri
    • , Giuseppe Pedrazzi
    • , Carolina Boni
    • , Marzia Rossi
    • , Andrea Vecchi
    • , Amalia Penna
    • , Alessandra Zecca
    • , Cristina Mori
    • , Alessandra Orlandini
    • , Elisa Negri
    • , Marco Pesci
    • , Marco Massari
    • , Gabriele Missale
    • , Massimo Levrero
    • , Simone Ottonello
    •  & 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
    • , Camille Sureau
    • , Susanne Müller
    • , Dulce Alfaiate
    • , Francesca Guerrieri
    • , Apirat Chaikuad
    • , Martin Schröder
    • , Philippe Merle
    • , Massimo Levrero
    •  & 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
    • , Delphine C. Malherbe
    • , Shilpi Pandey
    • , Jason Reed
    • , Eun Sung Yang
    • , Keyun Wang
    • , Amarendra Pegu
    • , Xuejun Chen
    • , Don Siess
    • , David Burke
    • , Heidi Henderson
    • , Rebecca Lewinsohn
    • , Miranda Fischer
    • , Jeffrey J. Stanton
    • , Michael K. Axthelm
    • , Christoph Kahl
    • , Byung Park
    • , Anne D. Lewis
    • , Jonah B. Sacha
    • , John R. Mascola
    • , Ann J. Hessell
    •  & 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
    • , Toshihide Ueno
    • , Yamato Fukui
    • , Emiko Yoshida
    • , Takuo Hayashi
    • , Shinya Kojima
    • , Reina Takeyama
    • , Taiki Hashimoto
    • , Tohru Kiyono
    • , Masako Ikemura
    • , Ayumi Taguchi
    • , Tomoki Tanaka
    • , Yosuke Tanaka
    • , Seiji Sakata
    • , Kengo Takeuchi
    • , Ayako Muraoka
    • , Satoko Osuka
    • , Tsuyoshi Saito
    • , Katsutoshi Oda
    • , Yutaka Osuga
    • , Yasuhisa Terao
    • , Masahito Kawazu
    •  & 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
    • , Thorsten Eierhoff
    • , Winfried Römer
    •  & 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
    • , Kazuki Takeda
    • , Yukihide Momozawa
    • , Hsing-Fang Lu
    • , Michiaki Kubo
    • , Yoichiro Kamatani
    • , Yoji Ogura
    • , Yohei Takahashi
    • , Masahiro Nakajima
    • , Shohei Minami
    • , Koki Uno
    • , Noriaki Kawakami
    • , Manabu Ito
    • , Ikuho Yonezawa
    • , Kei Watanabe
    • , Takashi Kaito
    • , Haruhisa Yanagida
    • , Hiroshi Taneichi
    • , Katsumi Harimaya
    • , Yuki Taniguchi
    • , Hideki Shigematsu
    • , Takahiro Iida
    • , Satoru Demura
    • , Ryo Sugawara
    • , Nobuyuki Fujita
    • , Mitsuru Yagi
    • , Eijiro Okada
    • , Naobumi Hosogane
    • , Katsuki Kono
    • , Masaya Nakamura
    • , Kazuhiro Chiba
    • , Toshiaki Kotani
    • , Tsuyoshi Sakuma
    • , Tsutomu Akazawa
    • , Teppei Suzuki
    • , Kotaro Nishida
    • , Kenichiro Kakutani
    • , Taichi Tsuji
    • , Hideki Sudo
    • , Akira Iwata
    • , Tatsuya Sato
    • , Satoshi Inami
    • , Morio Matsumoto
    • , Chikashi Terao
    • , Kota Watanabe
    •  & 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
    • , Xuyao Jiao
    • , Maria Lara-Tejero
    •  & 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
    • , Sally Teoh
    • , Adrienne Meyers
    • , John Ho
    • , T. Blake Ball
    • , Yoav Keynan
    • , Amarnath Pisipati
    • , Aseem Kumar
    • , Damon P. Eisen
    • , Kevin Lai
    • , Mark Gillett
    • , Rahul Santram
    • , Robert Geffers
    • , Jens Schreiber
    • , Khyobeni Mozhui
    • , Stephen Huang
    • , Grant P. Parnell
    • , Marek Nalos
    • , Monika Holubova
    • , Tracy Chew
    • , David Booth
    • , Anand Kumar
    • , Anthony McLean
    •  & 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
    • , Valentina Vongrad
    • , Teja Turk
    • , Kathrin Neumann
    • , Niko Beerenwinkel
    • , Jasmina Bogojeska
    • , Jaques Fellay
    • , Volker Roth
    • , Yik Lim Kok
    • , Christian W. Thorball
    • , Alessandro Borghesi
    • , Sonali Parbhoo
    • , Mario Wieser
    • , Jürg Böni
    • , Matthieu Perreau
    • , Thomas Klimkait
    • , Sabine Yerly
    • , Manuel Battegay
    • , Andri Rauch
    • , Matthias Hoffmann
    • , Enos Bernasconi
    • , Matthias Cavassini
    • , Roger D. Kouyos
    • , Huldrych F. Günthard
    • , Karin J. Metzner
    • , Alexia Anagnostopoulos
    • , Manuel Battegay
    • , Enos Bernasconi
    • , Jürg Böni
    • , Dominique L. Braun
    • , Heiner C. Bucher
    • , Alexandra Calmy
    • , Matthias Cavassini
    • , Angela Ciuffi
    • , Günter Dollenmaier
    • , Matthias Egger
    • , Luigia Elzi
    • , Jan Fehr
    • , Jacques Fellay
    • , Hansjakob Furrer
    • , Christoph A. Fux
    • , Huldrych F. Günthard
    • , David Haerry
    • , Barbara Hasse
    • , Hans H. Hirsch
    • , Matthias Hoffmann
    • , Irene Hösli
    • , Michael Huber
    • , Christian Kahlert
    • , Laurent Kaiser
    • , Olivia Keiser
    • , Thomas Klimkait
    • , Roger D. Kouyos
    • , Helen Kovari
    • , Bruno Ledergerber
    • , Gladys Martinetti
    • , Begona Martinez de Tejada
    • , Catia Marzolini
    • , Karin J. Metzner
    • , Nicolas Müller
    • , Dunja Nicca
    • , Paolo Paioni
    • , Guiseppe Pantaleo
    • , Matthieu Perreau
    • , Andri Rauch
    • , Christoph Rudin
    • , Alexandra U. Scherrer
    • , Patrick Schmid
    • , Roberto Speck
    • , Marcel Stöckle
    • , Philip Tarr
    • , Alexandra Trkola
    • , Pietro Vernazza
    • , Gilles Wandeler
    • , Rainer Weber
    •  & 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
    • , Sherin Pojar
    • , Simon P. Jochems
    • , Jesús Reiné
    • , Elissavet Nikolaou
    • , Carla Solórzano
    • , Mahdad Noursadeghi
    • , Jeremy S. Brown
    • , Daniela M. Ferreira
    •  & 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
    • , Naomi Song
    • , Temitope O. Nathan
    • , Benjamin M. Swarts
    • , Seok-Yong Eum
    • , Sabine Ehrt
    • , Sang-Nae Cho
    •  & Hyungjin Eoh
  • Article
    | Open Access

    Innate immune signaling pathways sense different microbial features and can elicit distinct yet overlapping immune responses. Here the authors dissect the contribution of these pathways to the response to MCMV infection and find that STING signaling is dispensable for host survival but crucial to restrict viral replication and dissemination via myeloid cells.

    • Pia-Katharina Tegtmeyer
    • , Julia Spanier
    • , Katharina Borst
    • , Jennifer Becker
    • , André Riedl
    • , Christoph Hirche
    • , Luca Ghita
    • , Jennifer Skerra
    • , Kira Baumann
    • , Stefan Lienenklaus
    • , Marius Doering
    • , Zsolt Ruzsics
    •  & Ulrich Kalinke
  • 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
    • , Shaozhuang Liu
    • , Yujie Zhang
    • , Chunmei Zhang
    • , Mi Tian
    • , Huixia Lu
    • , Peili Bu
    • , Jianmin Yang
    • , Changhan Ouyang
    • , Xiuxin Jiang
    • , Jiliang Wu
    • , Yun Zhang
    • , Qing Min
    • , Cheng Zhang
    •  & 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
    • , Joyce Mwongeli Ngoi
    • , Martin N. Mutunga
    • , Timothy Chege
    • , Elijah T. Gicheru
    • , Elizabeth M. Gardiner
    • , Agnes Gwela
    • , Christopher A. Green
    • , Simon B. Drysdale
    • , James A. Berkley
    • , D. James Nokes
    •  & 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
    • , Myra J. Chen
    • , Rajiv Dixit
    • , Lata Adnani
    • , Luke S. Frankiw
    • , Samuel O. Lawn
    • , Michael D. Blough
    • , Mana Alshehri
    • , Wei Wu
    • , Marco A. Marra
    • , Stephen M. Robbins
    • , J. Gregory Cairncross
    • , Carol Schuurmans
    •  & 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
    • , Tea Tsaava
    • , Adam M. Kressel
    • , Ileana Hancu
    • , Paul Fitzgerald
    • , Kirk Wallace
    • , Sireesha Kaanumalle
    • , John Graf
    • , Wayne Rigby
    • , Tzu-Jen Kao
    • , Jeanette Roberts
    • , Chitresh Bhushan
    • , Suresh Joel
    • , Thomas R. Coleman
    • , Stavros Zanos
    • , Kevin J. Tracey
    • , Jeffrey Ashe
    • , Sangeeta S. Chavan
    •  & 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
    • , Rachel S. Graham
    • , Yohan Kim
    • , Jerel Mueller
    • , Jennifer L. Auger
    • , Nathaniel J. Schuldt
    • , Claire R. W. Kaiser
    • , Abigail P. Heiller
    • , Raini Dutta
    • , Hongsun Guo
    • , Jamu K. Alford
    • , Bryce A. Binstadt
    •  & 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
    • , Nikolaj Pagh Kristensen
    • , Anne-Mette Bjerregaard
    • , Amalie Kai Bentzen
    • , Andrea Marion Marquard
    • , Tripti Tamhane
    • , Kristoffer Sølvsten Burgdorf
    • , Henrik Ullum
    • , Poul Jennum
    • , Stine Knudsen
    • , Sine Reker Hadrup
    •  & 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
    • , Zijuan Chen
    • , Lei Sun
    • , Juehui Wu
    • , Haohao Li
    • , Feng Liu
    • , Fei Wang
    • , Chunfu Yang
    • , Juhao Yang
    • , Qibin Leng
    • , Qingli Zhang
    • , Ajing Xu
    • , Lisong Shen
    • , Jinqiao Sun
    • , Dianqing Wu
    • , Caiyun Fang
    • , Haojie Lu
    • , Dapeng Yan
    •  & 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
    • , Chandima Jeewandara
    • , Geethal. S. Bandara Jayarathna
    • , Dhanushka Herath
    • , Pathum Asela Perera
    • , Samitha Fernando
    • , Ananda Wijewickrama
    • , Clare S. Hardman
    • , Graham S. Ogg
    •  & 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
    • , Lorena Preciado-Llanes
    • , Giorgio Napolitani
    • , Neil Ashley
    • , Adam Cribbs
    • , Jana Koth
    • , B. Christoffer Lagerholm
    • , Tim Ambrose
    • , Melita A. Gordon
    • , David Sims
    •  & 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
    • , Arne Burssens
    • , Peggy Jacques
    • , Nadia Schryvers
    • , Amélie De Muynck
    • , Leander Meuris
    • , Stijn Lambrecht
    • , Shea Carter
    • , Pieter de Bleser
    • , Yvan Saeys
    • , Luc Van Hoorebeke
    • , George Kollias
    • , Matthias Mack
    • , Paul Simoens
    • , Rik Lories
    • , Nico Callewaert
    • , Georg Schett
    •  & Dirk Elewaut
  • Article
    | Open Access

    How Mycobacterium tuberculosis (Mtb) escapes autophagy-mediated clearance is poorly understood. Here, Liu et al. show that Mtb-induced MicroRNA-27a targets the ER-associated calcium transporter CACNA2D3, leading to suppression of antimicrobial autophagy and to enhanced intracellular survival of Mtb.

    • Feng Liu
    • , Jianxia Chen
    • , Peng Wang
    • , Haohao Li
    • , Yilong Zhou
    • , Haipeng Liu
    • , Zhonghua Liu
    • , Ruijuan Zheng
    • , Lin Wang
    • , Hua Yang
    • , Zhenling Cui
    • , Fei Wang
    • , Xiaochen Huang
    • , Jie Wang
    • , Wei Sha
    • , Heping Xiao
    •  & Baoxue Ge
  • 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
    • , Andreas Beineke
    • , Xiaokun Liu
    • , Andreas Nerlich
    • , Kira van Vorst
    • , Manfred Rohde
    • , Ulrich Kalinke
    • , Reinhold Förster
    • , Stephan Halle
    • , Peter Valentin-Weigand
    • , Mathias W. Hornef
    •  & 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
    • , Kathleen E. McGrath
    • , Allison J. Li
    • , Benjamin J. Frisch
    • , James Palis
    • , Laura M. Calvi
    • , Yi Zhang
    •  & Archibald S. Perkins
  • Article
    | Open Access

    Salmonella serovars colonize a wide range of hosts but the underlying genetic determinants remain poorly understood. Here, Seif et al. use a network-based computational analysis to link specific metabolic capabilities with host range and nutritional niche.

    • Yara Seif
    • , Erol Kavvas
    • , Jean-Christophe Lachance
    • , James T. Yurkovich
    • , Sean-Paul Nuccio
    • , Xin Fang
    • , Edward Catoiu
    • , Manuela Raffatellu
    • , Bernhard O. Palsson
    •  & Jonathan M. Monk
  • 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
    • , Vicky Sender
    • , Laura Spelmink
    • , Marie-Stephanie Aschtgen
    • , Sandra Muschiol
    • , Jerker Widengren
    •  & 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
    • , Ru Zang
    • , Wen Ye
    • , Qing Yang
    • , Xia-Nan Zhang
    • , Yun-Da Chen
    • , Yu-Zhi Fu
    • , Ming-Ming Hu
    • , Cao-Qi Lei
    • , Wei-Wei Luo
    • , Shu Li
    •  & 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
    • , Kalliopi Thanopoulou
    • , Clara Baldin
    • , Elias Drakos
    • , Sameh S. M. Soliman
    • , Amol C. Shetty
    • , Carrie McCracken
    • , Tonia Akoumianaki
    • , Kostas Stylianou
    • , Petros Ioannou
    • , Charalampos Pontikoglou
    • , Helen A. Papadaki
    • , Maria Tzardi
    • , Valerie Belle
    • , Emilien Etienne
    • , Anne Beauvais
    • , George Samonis
    • , Dimitrios P. Kontoyiannis
    • , Evangelos Andreakos
    • , Vincent M. Bruno
    • , Ashraf S. Ibrahim
    •  & 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
    • , Sandrine Chantepie
    • , Stephan Sonntag
    • , Beyhan Tüysüz
    • , Ercan Mihci
    • , Christopher T. Gordon
    • , Elisabeth Steichen-Gersdorf
    • , Jeanne Amiel
    • , Banu Nur
    • , Irene Stolte-Dijkstra
    • , Albertien M. van Eerde
    • , Koen L. van Gassen
    • , Corstiaan C. Breugem
    • , Alexander Stegmann
    • , Caroline Lekszas
    • , Reza Maroofian
    • , Ehsan Ghayoor Karimiani
    • , Arnaud Bruneel
    • , Nathalie Seta
    • , Arnold Munnich
    • , Dulce Papy-Garcia
    • , Muriel De La Dure-Molla
    •  & 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
    • , Martin Jaeger
    • , Samuel M. Gonçalves
    • , R. K. Subbarao Malireddi
    • , Anne Ammerdorffer
    • , Rosalie Lubbers
    • , Marije Oosting
    • , Orhan Rasid
    • , Grégory Jouvion
    • , Catherine Fitting
    • , Dirk J. de Jong
    • , João F. Lacerda
    • , António Campos Jr.
    • , Willem J. G. Melchers
    • , Katrien Lagrou
    • , Johan Maertens
    • , Thirumala-Devi Kanneganti
    • , Agostinho Carvalho
    • , Oumaima Ibrahim-Granet
    •  & 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
    • , Lingmiao Kong
    • , Min Li
    • , Zhongxue Feng
    • , Bingxing Shuai
    • , Lijun Wang
    • , Yong’gang Wei
    • , Hongyu Li
    • , Sisi Wu
    • , Chun Tan
    • , Huan Zhao
    • , Xuejiao Hu
    • , Jin Liu
    • , Yan Kang
    • , Xuelian Liao
    • , Yan Zhou
    •  & Wei Zhang
  • Article
    | Open Access

    Bacteria respond to stresses using two-component systems consisting of sensor kinases (SKs) and response regulators. Here, Francis et al. reveal three specific interaction mechanisms between a pair of SKs that are important for regulation of virulence in the pathogen Pseudomonas aeruginosa.

    • Vanessa I. Francis
    • , Elaine M. Waters
    • , Sutharsan E. Finton-James
    • , Andrea Gori
    • , Aras Kadioglu
    • , Alan R. Brown
    •  & Steven L. Porter
  • Article
    | Open Access

    The effects of iron on vacuole-resident Salmonella in macrophages are unclear. Here the authors show that the bacteria are not subject to nutritional inhibition by iron deprivation, but that iron depletion in the vacuole, via the hepcidin-ferroportin axis, inhibits the bactericidal effect of oxidative burst.

    • Daejin Lim
    • , Kwang Soo Kim
    • , Jae-Ho Jeong
    • , Oriana Marques
    • , Hyun-Ju kim
    • , Miryoung Song
    • , Tae-Hoon Lee
    • , Jae Il Kim
    • , Hueng-Sik Choi
    • , Jung-Joon Min
    • , Dirk Bumann
    • , Martina U. Muckenthaler
    •  & Hyon E. Choy
  • 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
    • , Claire E. Hall
    • , Jamie S. Mitchell
    • , Helen Devine
    • , Doaa M. Taha
    • , Bilal Malik
    • , Ione Meyer
    • , Linda Greensmith
    • , Jia Newcombe
    • , Jernej Ule
    • , Nicholas M. Luscombe
    •  & Rickie Patani