Browse Articles

  • Article |

    The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.

    • Liang Ye
    • , Daniel Schnepf
    • , Jan Becker
    • , Karolina Ebert
    • , Yakup Tanriver
    • , Valentina Bernasconi
    • , Hans Henrik Gad
    • , Rune Hartmann
    • , Nils Lycke
    •  & Peter Staeheli
  • Article |

    The central nervous system meninges have a dense network of yolk sac–derived macrophages that serve a sentinel role. McGavern and colleagues show that this meningeal niche is replenished by bone marrow–derived inflammatory monocytes, which alters meningeal immune reactions after subsequent immune challenge.

    • Rejane Rua
    • , Jane Y. Lee
    • , Alexander B. Silva
    • , Isabella S. Swafford
    • , Dragan Maric
    • , Kory R. Johnson
    •  & Dorian B. McGavern
  • Article |

    Lymph fluid carries cells, debris and viruses to draining lymph nodes. Hickman and colleagues show that large viruses can enter lymph node conduits and gain access to dendritic cells positioned deep within lymph nodes for efficient presentation of antigen to CD8+ T cells.

    • Glennys V. Reynoso
    • , Andrea S. Weisberg
    • , John P. Shannon
    • , Daniel T. McManus
    • , Lucas Shores
    • , Jeffrey L. Americo
    • , Radu V. Stan
    • , Jonathan W. Yewdell
    •  & Heather D. Hickman
  • Publisher Correction |

    • Sarah A. Dick
    • , Jillian A. Macklin
    • , Sara Nejat
    • , Abdul Momen
    • , Xavier Clemente-Casares
    • , Marwan G. Althagafi
    • , Jinmiao Chen
    • , Crystal Kantores
    • , Siyavash Hosseinzadeh
    • , Laura Aronoff
    • , Anthony Wong
    • , Rysa Zaman
    • , Iulia Barbu
    • , Rickvinder Besla
    • , Kory J. Lavine
    • , Babak Razani
    • , Florent Ginhoux
    • , Mansoor Husain
    • , Myron I. Cybulsky
    • , Clinton S. Robbins
    •  & Slava Epelman
  • Publisher Correction |

    • Giorgio Napolitani
    • , Prathiba Kurupati
    • , Karen Wei Weng Teng
    • , Malick M. Gibani
    • , Margarida Rei
    • , Anna Aulicino
    • , Lorena Preciado-Llanes
    • , Michael Thomas Wong
    • , Etienne Becht
    • , Lauren Howson
    • , Paola de Haas
    • , Mariolina Salio
    • , Christoph J. Blohmke
    • , Lars Rønn Olsen
    • , David Miguel Susano Pinto
    • , Laura Scifo
    • , Claire Jones
    • , Hazel Dobinson
    • , Danielle Campbell
    • , Helene B. Juel
    • , Helena Thomaides-Brears
    • , Derek Pickard
    • , Dirk Bumann
    • , Stephen Baker
    • , Gordon Dougan
    • , Alison Simmons
    • , Melita A. Gordon
    • , Evan William Newell
    • , Andrew J. Pollard
    •  & Vincenzo Cerundolo
  • Article |

    Macrophages can shift their cellular metabolism in response to tissue cues and infection. Pearce and colleagues show that lipopolysaccharide-activated ‘inflammatory’ macrophages become depleted of NAD+ pools and require the salvage-pathway enzyme NAMPT to sustain cellular redox balance.

    • Alanna M. Cameron
    • , Angela Castoldi
    • , David E. Sanin
    • , Lea J. Flachsmann
    • , Cameron S. Field
    • , Daniel. J. Puleston
    • , Ryan L. Kyle
    • , Annette E. Patterson
    • , Fabian Hässler
    • , Joerg M. Buescher
    • , Beth Kelly
    • , Erika L. Pearce
    •  & Edward J. Pearce
  • News & Views |

    Recent studies indicate that macrophages utilize NAD+-biosynthetic pathways to control inflammation and cell survival during the immune response and aging.

    • Leah K. Billingham
    •  & Navdeep S. Chandel
  • News & Views |

    Inflammasomes have been reported to function in a wide variety of innate immune cells; however, their activity now seems to be more restricted than previously thought.

    • Pierre Guermonprez
    •  & Julie Helft
  • Technical Report |

    Determining TCR specificity represents a formidable technical barrier to the harnessing of T cell function. Kisielow and colleagues describe a novel platform for efficient determination of TCR specificities in a variety of infectious and cancer settings and in both human systems and mouse systems.

    • Jan Kisielow
    • , Franz-Josef Obermair
    •  & Manfred Kopf
  • News & Views |

    Members of the SLAM family of receptors promote the progression of invariant natural killer T cells through the thymic maturation process and facilitate proper host responses to exogenous lipid antigen through the recruitment and activity of SAP–Fyn and SHP-1, respectively.

    • Shankar S. Iyer
    • , Yu-Hwa Huang
    •  & Richard S. Blumberg
  • Article |

    Shulman and colleagues show that in contrast to events in lymph nodes and spleen, in Peyer’s patches, T cells promote B cell expansion without clonal selection during pre-germinal center events.

    • Adi Biram
    • , Anneli Strömberg
    • , Eitan Winter
    • , Liat Stoler-Barak
    • , Ran Salomon
    • , Yoseph Addadi
    • , Rony Dahan
    • , Gur Yaari
    • , Mats Bemark
    •  & Ziv Shulman
  • Resource |

    Interferon-stimulated genes (ISGs) are a key component of the antiviral response. Pichlmair and colleagues generate a comprehensive ISG interactome that sheds light on their functions in antiviral responses.

    • Philipp Hubel
    • , Christian Urban
    • , Valter Bergant
    • , William M. Schneider
    • , Barbara Knauer
    • , Alexey Stukalov
    • , Pietro Scaturro
    • , Angelika Mann
    • , Linda Brunotte
    • , Heinrich H. Hoffmann
    • , John W. Schoggins
    • , Martin Schwemmle
    • , Matthias Mann
    • , Charles M. Rice
    •  & Andreas Pichlmair
  • Article |

    Removal of damaged mitochondria maintains cellular homeostasis and regulates inflammation. Qian and colleagues describe a mechanism by which intracellular bacteria such as Listeria can elicit mitophagy to enable their survival.

    • Yifan Zhang
    • , Yikun Yao
    • , Xiaoxu Qiu
    • , Guodong Wang
    • , Zheng Hu
    • , Siyuan Chen
    • , Zhengxi Wu
    • , Na Yuan
    • , Hanchao Gao
    • , Jianrong Wang
    • , Houhui Song
    • , Stephen E. Girardin
    •  & Youcun Qian
  • Article |

    Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.

    • Clémence Hollande
    • , Jeremy Boussier
    • , James Ziai
    • , Tamaki Nozawa
    • , Vincent Bondet
    • , Wilson Phung
    • , Binfeng Lu
    • , Darragh Duffy
    • , Valerie Paradis
    • , Vincent Mallet
    • , Gérard Eberl
    • , Wendy Sandoval
    • , Jill M. Schartner
    • , Stanislas Pol
    • , Rosa Barreira da Silva
    •  & Matthew L. Albert
  • Article |

    Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

    • Brian C. Miller
    • , Debattama R. Sen
    • , Rose Al Abosy
    • , Kevin Bi
    • , Yamini V. Virkud
    • , Martin W. LaFleur
    • , Kathleen B. Yates
    • , Ana Lako
    • , Kristen Felt
    • , Girish S. Naik
    • , Michael Manos
    • , Evisa Gjini
    • , Juhi R. Kuchroo
    • , Jeffrey J. Ishizuka
    • , Jenna L. Collier
    • , Gabriel K. Griffin
    • , Seth Maleri
    • , Dawn E. Comstock
    • , Sarah A. Weiss
    • , Flavian D. Brown
    • , Arpit Panda
    • , Margaret D. Zimmer
    • , Robert T. Manguso
    • , F. Stephen Hodi
    • , Scott J. Rodig
    • , Arlene H. Sharpe
    •  & W. Nicholas Haining
  • Technical Report |

    It remains difficult to distinguish cognate APC–T cell interactions in human tissue sections. Clark and colleagues have developed an imaging–machine-learning pipeline that uses deep convolutional and tuned neural networks to identify the combination of distance and cell-shape features that can discriminate between bystander human APC–T cell interactions and cognate interactions in situ.

    • Vladimir M. Liarski
    • , Adam Sibley
    • , Nicholas van Panhuys
    • , Junting Ai
    • , Anthony Chang
    • , Domenick Kennedy
    • , Maria Merolle
    • , Ronald N. Germain
    • , Maryellen L. Giger
    •  & Marcus R. Clark
  • News & Views |

    Combined immunotherapy using checkpoint blockade (anti-CTLA4 and anti-PD-1) and the DPP4 inhibitor sitagliptin reveals the existence of a T cell– and eosinophil-targeted immunotherapy approach for solid tumors.

    • Ariel Munitz
    •  & Simon Patrick Hogan
  • Article |

    Stemness is crucial for the maintenance of long-term T cell memory. Gattinoni and colleagues demonstrate that the transcription factor c-Myb is essential for the establishment of a stemness program in the CD8+ T cell memory compartment.

    • Sanjivan Gautam
    • , Jessica Fioravanti
    • , Wei Zhu
    • , John B. Le Gall
    • , Philip Brohawn
    • , Neal E. Lacey
    • , Jinhui Hu
    • , James D. Hocker
    • , Nga Voong Hawk
    • , Veena Kapoor
    • , William G. Telford
    • , Devikala Gurusamy
    • , Zhiya Yu
    • , Avinash Bhandoola
    • , Hai-Hui Xue
    • , Rahul Roychoudhuri
    • , Brandon W. Higgs
    • , Nicholas P. Restifo
    • , Timothy P. Bender
    • , Yun Ji
    •  & Luca Gattinoni
  • Article |

    Cross-protective responses across all strains of influenza virus (IAV, IBV and ICV) are a key goal of universal vaccines against influenza. Kedzierska and colleagues identify cytotoxic T cells present in blood and lungs of healthy people that are directed against all strains of influenza virus.

    • Marios Koutsakos
    • , Patricia T. Illing
    • , Thi H. O. Nguyen
    • , Nicole A. Mifsud
    • , Jeremy Chase Crawford
    • , Simone Rizzetto
    • , Auda A. Eltahla
    • , E. Bridie Clemens
    • , Sneha Sant
    • , Brendon Y. Chua
    • , Chinn Yi Wong
    • , E. Kaitlynn Allen
    • , Don Teng
    • , Pradyot Dash
    • , David F. Boyd
    • , Ludivine Grzelak
    • , Weiguang Zeng
    • , Aeron C. Hurt
    • , Ian Barr
    • , Steve Rockman
    • , David C. Jackson
    • , Tom C. Kotsimbos
    • , Allen C. Cheng
    • , Michael Richards
    • , Glen P. Westall
    • , Thomas Loudovaris
    • , Stuart I. Mannering
    • , Michael Elliott
    • , Stuart G. Tangye
    • , Linda M. Wakim
    • , Jamie Rossjohn
    • , Dhanasekaran Vijaykrishna
    • , Fabio Luciani
    • , Paul G. Thomas
    • , Stephanie Gras
    • , Anthony W. Purcell
    •  & Katherine Kedzierska
  • Article |

    An intricately linked homeostasis exists between the gut microbiome and host immune system. Scheffold and colleagues show that intestinal Treg cells upregulate the transcription factor c-Maf in response to specific signals from the gut microenvironment to establish host–microbiota homeostasis.

    • Christian Neumann
    • , Jonas Blume
    • , Urmi Roy
    • , Peggy P. Teh
    • , Ajithkumar Vasanthakumar
    • , Alexander Beller
    • , Yang Liao
    • , Frederik Heinrich
    • , Teresita L. Arenzana
    • , Jason A. Hackney
    • , Celine Eidenschenk
    • , Eric J. C. Gálvez
    • , Christina Stehle
    • , Gitta A. Heinz
    • , Patrick Maschmeyer
    • , Tom Sidwell
    • , Yifang Hu
    • , Derk Amsen
    • , Chiara Romagnani
    • , Hyun-Dong Chang
    • , Andrey Kruglov
    • , Mir-Farzin Mashreghi
    • , Wei Shi
    • , Till Strowig
    • , Sascha Rutz
    • , Axel Kallies
    •  & Alexander Scheffold
  • News & Views |

    A multivalent vaccine that presents diverse influenza virus subtype H1 hemagglutinins on its surface induces broadly neutralizing antibodies in an animal model by displaying conserved epitopes at higher density than strain-specific epitopes.

    • Florian Krammer
  • Letter |

    Dendritic cells (DCs) have been suggested to express a functional NLRP3 inflammasome. Gerlic and colleagues demonstrate, however, that bone marrow–derived DCs completely lack NLRP3 inflammasome activity and that the bulk of splenic DCs lack or have only minimal activity.

    • Ziv Erlich
    • , Inbar Shlomovitz
    • , Liat Edry-Botzer
    • , Hadar Cohen
    • , Daniel Frank
    • , Hanqing Wang
    • , Andrew M. Lew
    • , Kate E. Lawlor
    • , Yifan Zhan
    • , James E. Vince
    •  & Motti Gerlic
  • Article |

    Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

    • Masaru Kanekiyo
    • , M. Gordon Joyce
    • , Rebecca A. Gillespie
    • , John R. Gallagher
    • , Sarah F. Andrews
    • , Hadi M. Yassine
    • , Adam K. Wheatley
    • , Brian E. Fisher
    • , David R. Ambrozak
    • , Adrian Creanga
    • , Kwanyee Leung
    • , Eun Sung Yang
    • , Seyhan Boyoglu-Barnum
    • , Ivelin S. Georgiev
    • , Yaroslav Tsybovsky
    • , Madhu S. Prabhakaran
    • , Hanne Andersen
    • , Wing-Pui Kong
    • , Ulrich Baxa
    • , Kathryn L. Zephir
    • , Julie E. Ledgerwood
    • , Richard A. Koup
    • , Peter D. Kwong
    • , Audray K. Harris
    • , Adrian B. McDermott
    • , John R. Mascola
    •  & Barney S. Graham
  • News & Views |

    The transition of the fetus from the womb to the external world represents an extraordinary challenge. The generation of memory T cells before birth may serve an important role in preparation for this fundamental transition.

    • Ai Ing Lim
    • , Oliver J. Harrison
    •  & Yasmine Belkaid
  • Publisher Correction |

    • Leona Gabryšová
    • , Marisol Alvarez-Martinez
    • , Raphaëlle Luisier
    • , Luke S. Cox
    • , Jan Sodenkamp
    • , Caroline Hosking
    • , Damián Pérez-Mazliah
    • , Charlotte Whicher
    • , Yashaswini Kannan
    • , Krzysztof Potempa
    • , Xuemei Wu
    • , Leena Bhaw
    • , Hagen Wende
    • , Michael H. Sieweke
    • , Greg Elgar
    • , Mark Wilson
    • , James Briscoe
    • , Vicki Metzis
    • , Jean Langhorne
    • , Nicholas M. Luscombe
    •  & Anne O’Garra
  • Author Correction |

    • Jake Dunning
    • , Simon Blankley
    • , Long T. Hoang
    • , Mike Cox
    • , Christine M. Graham
    • , Philip L. James
    • , Chloe I. Bloom
    • , Damien Chaussabel
    • , Jacques Banchereau
    • , Stephen J. Brett
    • , Maximillian S. Habibi
    • , Sebastian L. Johnston
    • , Trevor T. Hansel
    • , Mike Levin
    • , Ryan S. Thwaites
    • , John O. Warner
    • , William O. Cookson
    • , Brian G. Gazzard
    • , Alan Hay
    • , John McCauley
    • , Paul Aylin
    • , Deborah Ashby
    • , Wendy S. Barclay
    • , Ruth A. Elderfield
    • , Simon Nadel
    • , Jethro A. Herberg
    • , Lydia N. Drumright
    • , Laura Garcia-Alvarez
    • , Alison H. Holmes
    • , Onn M. Kon
    • , Stephen J. Aston
    • , Stephen B. Gordon
    • , Tracy Hussell
    • , Catherine Thompson
    • , Maria C. Zambon
    • , Kenneth J. Baillie
    • , David A. Hume
    • , Peter Simmonds
    • , Andrew Hayward
    • , Rosalind L. Smyth
    • , Paul S. McNamara
    • , Malcolm G. Semple
    • , Jonathan S. Nguyen-Van-Tam
    • , Ling-Pei Ho
    • , Andrew J. McMichael
    • , Paul Kellam
    • , Walt E Adamson
    • , William F Carman
    • , Mark J. Griffiths
    • , Miriam F. Moffatt
    • , Anne O’Garra
    •  & Peter J. M. Openshaw
  • Article |

    Pathogenic human CD4+ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.

    • Zhenke Wen
    • , Ke Jin
    • , Yi Shen
    • , Zhen Yang
    • , Yinyin Li
    • , Bowen Wu
    • , Lu Tian
    • , Stanford Shoor
    • , Niall E. Roche
    • , Jorg J. Goronzy
    •  & Cornelia M. Weyand
  • News & Views |

    The zinc transporter ZIP7 positively regulates signaling via the BCR during early B cell development in mice and humans. Impairment of ZIP7 function results in a novel primary immunodeficiency.

    • Toshiyuki Fukada
    • , Shintaro Hojyo
    • , Takafumi Hara
    •  & Teruhisa Takagishi
  • News & Views |

    In patients with rheumatoid arthritis, decreased abundance of the N-myristoyltransferase NMT1 in CD4+ T cells prevents N-myristoylation of the AMP-activated protein kinase AMPK and its localization to the lysosomal membrane, which leads to increased activation of the metabolic checkpoint kinase complex mTORC1 and proinflammatory T cell phenotypes.

    • David K. Finlay
  • Article |

    Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.

    • Consuelo Anzilotti
    • , David J. Swan
    • , Bertrand Boisson
    • , Mukta Deobagkar-Lele
    • , Catarina Oliveira
    • , Pauline Chabosseau
    • , Karin R. Engelhardt
    • , Xijin Xu
    • , Rui Chen
    • , Luis Alvarez
    • , Rolando Berlinguer-Palmini
    • , Katherine R. Bull
    • , Eleanor Cawthorne
    • , Adam P. Cribbs
    • , Tanya L. Crockford
    • , Tarana Singh Dang
    • , Amy Fearn
    • , Emma J. Fenech
    • , Sarah J. de Jong
    • , B. Christoffer Lagerholm
    • , Cindy S. Ma
    • , David Sims
    • , Bert van den Berg
    • , Yaobo Xu
    • , Andrew J. Cant
    • , Gary Kleiner
    • , T. Ronan Leahy
    • , M. Teresa de la Morena
    • , Jennifer M. Puck
    • , Ralph S. Shapiro
    • , Mirjam van der Burg
    • , J. Ross Chapman
    • , John C. Christianson
    • , Benjamin Davies
    • , John A. McGrath
    • , Stefan Przyborski
    • , Mauro Santibanez Koref
    • , Stuart G. Tangye
    • , Andreas Werner
    • , Guy A. Rutter
    • , Sergi Padilla-Parra
    • , Jean-Laurent Casanova
    • , Richard J. Cornall
    • , Mary Ellen Conley
    •  & Sophie Hambleton
  • Article |

    Serpins are a large family of serine protease inhibitors. Jae Jung and colleagues show that SERPINB1 serves an endogenous regulatory role for pro-inflammatory caspases by preventing CARD–CARD polymerization and, hence, inflammasome activation.

    • Youn Jung Choi
    • , Stephanie Kim
    • , Younho Choi
    • , Travis B. Nielsen
    • , Jun Yan
    • , Alvin Lu
    • , Jianbin Ruan
    • , Hye-Ra Lee
    • , Hao Wu
    • , Brad Spellberg
    •  & Jae U. Jung
  • Article |

    Tissue-resident memory T cells (TRM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal TRM cells can also have key pathogenic roles in inflammatory bowel disease.

    • Sebastian Zundler
    • , Emily Becker
    • , Marta Spocinska
    • , Monique Slawik
    • , Loreto Parga-Vidal
    • , Regina Stark
    • , Maximilian Wiendl
    • , Raja Atreya
    • , Timo Rath
    • , Moritz Leppkes
    • , Kai Hildner
    • , Rocío López-Posadas
    • , Sören Lukassen
    • , Arif B. Ekici
    • , Clemens Neufert
    • , Imke Atreya
    • , Klaas P. J. M. van Gisbergen
    •  & Markus F. Neurath
  • News & Views |

    A new target for controlling T cell responses adds to the list of key processes dependent on the synthesis of tetrahydrobiopterin, which is essential for neurotransmitter and nitric-oxide production and pain control.

    • Andrew L. Mellor
    •  & Lei Huang