Immunology

  • Article
    | Open Access

    Over 100 million of opioid prescriptions are issued yearly in the USA alone, but the impact of opioid use on the immune system is barely characterized. Here the authors report antiviral immune response is blunted in several types of blood cells from opioid-dependent individuals, and when healthy donor cells are exposed to morphine in a dish.

    • Tanya T. Karagiannis
    • , John P. Cleary Jr
    • , Busra Gok
    • , Andrew J. Henderson
    • , Nicholas G. Martin
    • , Masanao Yajima
    • , Elliot C. Nelson
    •  & Christine S. Cheng
  • Article
    | Open Access

    Poly-functional helper T cells can have a stronger effect than mono-functional T cells, but whether the response is qualitatively different is not clear. Here the authors show that a population of IL-17+IL-22+, but not single IL-22+, CD4+ T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice.

    • Laura Garcia Perez
    • , Jan Kempski
    • , Heather M. McGee
    • , Penelope Pelzcar
    • , Theodora Agalioti
    • , Anastasios Giannou
    • , Leonie Konczalla
    • , Leonie Brockmann
    • , Ramez Wahib
    • , Hao Xu
    • , Maria Carolina Amezcua Vesely
    • , Shiwa Soukou
    • , Babett Steglich
    • , Tanja Bedke
    • , Carolin Manthey
    • , Oliver Seiz
    • , Björn-Philipp Diercks
    • , Stylianos Gnafakis
    • , Andreas H. Guse
    • , Daniel Perez
    • , Jakob R. Izbicki
    • , Nicola Gagliani
    • , Richard A. Flavell
    •  & Samuel Huber
  • Article
    | Open Access

    Memory B cells are important for protecting the host from pathogen rechallenge, but their properties and locations remain ill-defined. Here the authors show, using single-cell transcriptomics and repertoire analyses, that mouse spleen and bone marrow host distinct populations of isotype-switched memory B cells to potentially optimize for rapid recall responses.

    • René Riedel
    • , Richard Addo
    • , Marta Ferreira-Gomes
    • , Gitta Anne Heinz
    • , Frederik Heinrich
    • , Jannis Kummer
    • , Victor Greiff
    • , Daniel Schulz
    • , Cora Klaeden
    • , Rebecca Cornelis
    • , Ulrike Menzel
    • , Stefan Kröger
    • , Ulrik Stervbo
    • , Ralf Köhler
    • , Claudia Haftmann
    • , Silvia Kühnel
    • , Katrin Lehmann
    • , Patrick Maschmeyer
    • , Mairi McGrath
    • , Sandra Naundorf
    • , Stefanie Hahne
    • , Özen Sercan-Alp
    • , Francesco Siracusa
    • , Jonathan Stefanowski
    • , Melanie Weber
    • , Kerstin Westendorf
    • , Jakob Zimmermann
    • , Anja E. Hauser
    • , Sai T. Reddy
    • , Pawel Durek
    • , Hyun-Dong Chang
    • , Mir-Farzin Mashreghi
    •  & Andreas Radbruch
  • Article
    | Open Access

    T cells recognize peptide antigens presented in the context of MHC but can additionally recognize non-conventional ligands. Here the authors show T cells specific for a HIV-1 associated glycopeptide antigen presented by MHC class II help envelope (Env) trimer induced humoral immune responses.

    • Lina Sun
    • , Amy V. Paschall
    • , Dustin R. Middleton
    • , Mayumi Ishihara
    • , Ahmet Ozdilek
    • , Paeton L. Wantuch
    • , Javid Aceil
    • , Jeremy A. Duke
    • , Celia C. LaBranche
    • , Michael Tiemeyer
    •  & Fikri Y. Avci
  • Article
    | Open Access

    The characteristics of immune cells in the peripheral nervous system (PNS) are not fully understood. Here the authors examine the transcriptomic profile and ontogeny of macrophages from the PNS, show they are derived from both embryonic and hematopoietic precursors, and that they have some shared features with microglia.

    • Peter L. Wang
    • , Aldrin K. Y. Yim
    • , Ki-Wook Kim
    • , Denis Avey
    • , Rafael S. Czepielewski
    • , Marco Colonna
    • , Jeffrey Milbrandt
    •  & Gwendalyn J. Randolph
  • Article
    | Open Access

    There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

    • Trevor R. F. Smith
    • , Ami Patel
    • , Stephanie Ramos
    • , Dustin Elwood
    • , Xizhou Zhu
    • , Jian Yan
    • , Ebony N. Gary
    • , Susanne N. Walker
    • , Katherine Schultheis
    • , Mansi Purwar
    • , Ziyang Xu
    • , Jewell Walters
    • , Pratik Bhojnagarwala
    • , Maria Yang
    • , Neethu Chokkalingam
    • , Patrick Pezzoli
    • , Elizabeth Parzych
    • , Emma L. Reuschel
    • , Arthur Doan
    • , Nicholas Tursi
    • , Miguel Vasquez
    • , Jihae Choi
    • , Edgar Tello-Ruiz
    • , Igor Maricic
    • , Mamadou A. Bah
    • , Yuanhan Wu
    • , Dinah Amante
    • , Daniel H. Park
    • , Yaya Dia
    • , Ali Raza Ali
    • , Faraz I. Zaidi
    • , Alison Generotti
    • , Kevin Y. Kim
    • , Timothy A. Herring
    • , Sophia Reeder
    • , Viviane M. Andrade
    • , Karen Buttigieg
    • , Gan Zhao
    • , Jiun-Ming Wu
    • , Dan Li
    • , Linlin Bao
    • , Jiangning Liu
    • , Wei Deng
    • , Chuan Qin
    • , Ami Shah Brown
    • , Makan Khoshnejad
    • , Nianshuang Wang
    • , Jacqueline Chu
    • , Daniel Wrapp
    • , Jason S. McLellan
    • , Kar Muthumani
    • , Bin Wang
    • , Miles W. Carroll
    • , J. Joseph Kim
    • , Jean Boyer
    • , Daniel W. Kulp
    • , Laurent M. P. F. Humeau
    • , David B. Weiner
    •  & Kate E. Broderick
  • Article
    | Open Access

    Nodular lymphocyte-predominant Hodgkin lymphoma with IgD+ lymphocyte-predominant (LP) cells is a rare clinical distinct lymphoma subset of B-cell origin. Here the authors show that antigens expressed by Moraxella catarrhalis are recognized by B cell receptors of IgD+ LP cells, suggesting the contribution of chronic antigen stimulation to lymphomagenesis.

    • Lorenz Thurner
    • , Sylvia Hartmann
    • , Natalie Fadle
    • , Evi Regitz
    • , Maria Kemele
    • , Yoo-Jin Kim
    • , Rainer Maria Bohle
    • , Anna Nimmesgern
    • , Lutz von Müller
    • , Volkhard A. J. Kempf
    • , Marc A. Weniger
    • , Frank Neumann
    • , Nadine Schneider
    • , Martine Vornanen
    • , Christer Sundström
    • , Laurence de Leval
    • , Andreas Engert
    • , Dennis A. Eichenauer
    • , Ralf Küppers
    • , Klaus-Dieter Preuss
    • , Martin-Leo Hansmann
    •  & Michael Pfreundschuh
  • Article
    | Open Access

    Type 1 diabetes is associated with autoimmune destruction of pancreatic beta-cells. Here the authors compose a large-scale electron microscopy image data base of pancreatic organ donor tissue to enable data mining and further understanding of the disease.

    • Pascal de Boer
    • , Nicole M. Pirozzi
    • , Anouk H. G. Wolters
    • , Jeroen Kuipers
    • , Irina Kusmartseva
    • , Mark A. Atkinson
    • , Martha Campbell-Thompson
    •  & Ben N. G. Giepmans
  • Article
    | Open Access

    Senotherapy, the removal of aged T cells, is an effective approach to attenuate age-related diseases. Here the authors report a CD153 targeting vaccine that prevents the accumulation of senescent adipose tissue T cells in mice on high-fat diet, which is associated with improved glucose tolerance.

    • Shota Yoshida
    • , Hironori Nakagami
    • , Hiroki Hayashi
    • , Yuka Ikeda
    • , Jiao Sun
    • , Akiko Tenma
    • , Hideki Tomioka
    • , Tomohiro Kawano
    • , Munehisa Shimamura
    • , Ryuichi Morishita
    •  & Hiromi Rakugi
  • Article
    | Open Access

    Vaccine mismatch and changes in antigenicity due to vaccine strain egg adaptation can affect seasonal influenza vaccine effectiveness. Here, Gouma et al. show that the egg-adapted 3c3.A H3N2 vaccine strain elicits antibodies with limited reactivity to a wildtype 3c3.A strain and currently circulating 3c2.A H3N2 strains.

    • Sigrid Gouma
    • , Madison Weirick
    •  & Scott E. Hensley
  • Article
    | Open Access

    Zika virus (ZIKV) poses a significant public health threat, but the immune landscape changes following ZIKV infection is still unclear. Here, the authors show, using flow cytometry and transcriptomic data, that ZIKV induces a multitude of immune responses, with plasmacytoid dendritic cells poised centrally to interact with other immune cell types.

    • Xiaoming Sun
    • , Stephane Hua
    • , Ce Gao
    • , Jane E. Blackmer
    • , Zhengyu Ouyang
    • , Kevin Ard
    • , Andrea Ciaranello
    • , Sigal Yawetz
    • , Paul E. Sax
    • , Eric S. Rosenberg
    • , Mathias Lichterfeld
    •  & Xu G. Yu
  • Article
    | Open Access

    The role of sexual practice in HIV-associated gut microbiota remains poorly understood. Here, in a cohort of chronically treated HIV-infected people, the authors show microbiome signatures to be independent of sex and sexual practice and that the extent of dysbiosis correlates with nadir CD4, inflammatory markers, and comorbidities.

    • I. Vujkovic-Cvijin
    • , O. Sortino
    • , E. Verheij
    • , J. Sklar
    • , F. W. Wit
    • , N. A. Kootstra
    • , B. Sellers
    • , J. M. Brenchley
    • , J. Ananworanich
    • , M. Schim van der Loeff
    • , Y. Belkaid
    • , P. Reiss
    •  & I. Sereti
  • Article
    | Open Access

    Neutrophils mobilize rapidly and travel through the vasculature and microcirculation en masse in response to inflammatory stimuli. Here the authors use a microfluidic device and intravital microscopy to show neutrophils move through tissues in a highly ordered pattern, taking turns to file into alternate branches at bifurcations.

    • Xiao Wang
    • , Mokarram Hossain
    • , Ania Bogoslowski
    • , Paul Kubes
    •  & Daniel Irimia
  • Article
    | Open Access

    Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14+Sirpα+ DC population that is capable of inducing Treg for establishing tolerance.

    • Matouš Vobořil
    • , Tomáš Brabec
    • , Jan Dobeš
    • , Iva Šplíchalová
    • , Jiří Březina
    • , Adéla Čepková
    • , Martina Dobešová
    • , Aigerim Aidarova
    • , Jan Kubovčiak
    • , Oksana Tsyklauri
    • , Ondřej Štěpánek
    • , Vladimír Beneš
    • , Radislav Sedláček
    • , Ludger Klein
    • , Michal Kolář
    •  & Dominik Filipp
  • Article
    | Open Access

    Extracellular vesicles can carry immunoregulatory cytokines such as TGF-β. Here the authors use CD11b-deficient mice and macrophages to show that such vesicles carrying TGF-β are produced in response to Candida albicans infections and can limit the proinflammatory response partly via a positive feedback on TGF-β production by endothelial cells.

    • Luke D. Halder
    • , Emeraldo A. H. Jo
    • , Mohammad Z. Hasan
    • , Marta Ferreira-Gomes
    • , Thomas Krüger
    • , Martin Westermann
    • , Diana I. Palme
    • , Günter Rambach
    • , Niklas Beyersdorf
    • , Cornelia Speth
    • , Ilse D. Jacobsen
    • , Olaf Kniemeyer
    • , Berit Jungnickel
    • , Peter F. Zipfel
    •  & Christine Skerka
  • Article
    | Open Access

    Recombinant T-cells receptors can redirect naïve T cells but often have low or uneven expression. Here, the authors model mutations in TCR constant domains to increase T cell receptor expression, assembly, and stability and generate bispecific molecules.

    • Karen Froning
    • , Jack Maguire
    • , Arlene Sereno
    • , Flora Huang
    • , Shawn Chang
    • , Kenneth Weichert
    • , Anton J. Frommelt
    • , Jessica Dong
    • , Xiufeng Wu
    • , Heather Austin
    • , Elaine M. Conner
    • , Jonathan R. Fitchett
    • , Aik Roy Heng
    • , Deepa Balasubramaniam
    • , Mark T. Hilgers
    • , Brian Kuhlman
    •  & Stephen J. Demarest
  • Article
    | Open Access

    Sepsis due to multidrug resistant pathogens is the most common cause of death in intensive care units. Here, the authors report that fecal microbiota transplant (FMT) can rescue mice from lethal sepsis of pathogens isolated from stool of a critically ill patient and show that FMT reverses the immunosuppressive effect induced by the pathogen community.

    • Sangman M. Kim
    • , Jennifer R. DeFazio
    • , Sanjiv K. Hyoju
    • , Kishan Sangani
    • , Robert Keskey
    • , Monika A. Krezalek
    • , Nikolai N. Khodarev
    • , Naseer Sangwan
    • , Scott Christley
    • , Katharine G. Harris
    • , Ankit Malik
    • , Alexander Zaborin
    • , Romain Bouziat
    • , Diana R. Ranoa
    • , Mara Wiegerinck
    • , Jordan D. Ernest
    • , Baddr A. Shakhsheer
    • , Irma D. Fleming
    • , Ralph R. Weichselbaum
    • , Dionysios A. Antonopoulos
    • , Jack A. Gilbert
    • , Luis B. Barreiro
    • , Olga Zaborina
    • , Bana Jabri
    •  & John C. Alverdy
  • Article
    | Open Access

    Inflammasome activation is a response to bacterial infection but can cause damage and spread infection. Here, the authors use live single-cell imaging to show two mechanisms by which M. tuberculosis causes damage to human macrophage cell plasma membranes, resulting in activation of the NLRP3 inflammasome, pyroptosis and release of infectious particles.

    • Kai S. Beckwith
    • , Marianne S. Beckwith
    • , Sindre Ullmann
    • , Ragnhild S. Sætra
    • , Haelin Kim
    • , Anne Marstad
    • , Signe E. Åsberg
    • , Trine A. Strand
    • , Markus Haug
    • , Michael Niederweis
    • , Harald A. Stenmark
    •  & Trude H. Flo
  • Article
    | Open Access

    Upon infection with cytomegalovirus, CD8+ T cells undergo prolific expansion in a process known as memory inflation. Here the authors define a population of Tcf1 expressing cells within the inflationary pool that is critical in fuelling this process.

    • Suzanne P. M. Welten
    • , Alexander Yermanos
    • , Nicolas S. Baumann
    • , Franziska Wagen
    • , Nathalie Oetiker
    • , Ioana Sandu
    • , Alessandro Pedrioli
    • , Jennifer D. Oduro
    • , Sai T. Reddy
    • , Luka Cicin-Sain
    • , Werner Held
    •  & Annette Oxenius
  • Article
    | Open Access

    Renal macrophages (RMs) can be of bone marrow or embryonic origin, but their abundance, fate and metabolic profiles in physiological and pathogenic settings are still unclear. Here the authors show, by characterizing these two RMs in multiple transgenic mouse lines, that they exhibit distinct dynamics, homeostasis, immune activity, and metabolic properties.

    • Fengming Liu
    • , Shen Dai
    • , Dechun Feng
    • , Zhongnan Qin
    • , Xiao Peng
    • , Siva S. V. P. Sakamuri
    • , Mi Ren
    • , Li Huang
    • , Min Cheng
    • , Kabir E. Mohammad
    • , Ping Qu
    • , Yong Chen
    • , Chunling Zhao
    • , Faliang Zhu
    • , Shujian Liang
    • , Bertal H. Aktas
    • , Xiaofeng Yang
    • , Hong Wang
    • , Prasad V. G. Katakam
    • , David W. Busija
    • , Tracy Fischer
    • , Prasun K. Datta
    • , Jay Rappaport
    • , Bin Gao
    •  & Xuebin Qin
  • Article
    | Open Access

    Macrophage activation is integral to innate immunity and inflammation, and involves transcriptome remodeling leading to the rapid upregulation of pro- and anti-inflammatory effector genes. Here the authors show that the negative elongation factor (NELF) complex controls the transcription of anti-inflammatory genes through Pol II pause release.

    • Li Yu
    • , Bin Zhang
    • , Dinesh Deochand
    • , Maria A. Sacta
    • , Maddalena Coppo
    • , Yingli Shang
    • , Ziyi Guo
    • , Xiaomin Zeng
    • , David A. Rollins
    • , Bowranigan Tharmalingam
    • , Rong Li
    • , Yurii Chinenov
    • , Inez Rogatsky
    •  & Xiaoyu Hu
  • Article
    | Open Access

    One cause of relapse in cancer patients treated with chimeric antigen receptor (CAR) T cells is the loss of CAR-targeted antigens, which is particularly common in multiple myeloma (MM). Here the authors engineer a CAR recognizing two common MM-associated antigens and demonstrate its superiority to single-antigen CARs in a mouse model of MM.

    • Eugenia Zah
    • , Eunwoo Nam
    • , Vinya Bhuvan
    • , Uyen Tran
    • , Brenda Y. Ji
    • , Stanley B. Gosliner
    • , Xiuli Wang
    • , Christine E. Brown
    •  & Yvonne Y. Chen
  • Article
    | Open Access

    Macrophages undergo a Warburg-like switch from oxidative phosphorylation to glycolysis in response to inflammatory stimulus. Here the authors show that fungal melanin can trigger this switch in human macrophages by sequestering calcium in the phagosome and enabling protection against Aspergillus fumigatus infection.

    • Samuel M. Gonçalves
    • , Cláudio Duarte-Oliveira
    • , Cláudia F. Campos
    • , Vishukumar Aimanianda
    • , Rob ter Horst
    • , Luis Leite
    • , Toine Mercier
    • , Paulo Pereira
    • , Miguel Fernández-García
    • , Daniela Antunes
    • , Cláudia S. Rodrigues
    • , Catarina Barbosa-Matos
    • , Joana Gaifem
    • , Inês Mesquita
    • , António Marques
    • , Nuno S. Osório
    • , Egídio Torrado
    • , Fernando Rodrigues
    • , Sandra Costa
    • , Leo AB. Joosten
    • , Katrien Lagrou
    • , Johan Maertens
    • , João F. Lacerda
    • , António Campos Jr.
    • , Gordon D. Brown
    • , Axel A. Brakhage
    • , Coral Barbas
    • , Ricardo Silvestre
    • , Frank L. van de Veerdonk
    • , Georgios Chamilos
    • , Mihai G. Netea
    • , Jean-Paul Latgé
    • , Cristina Cunha
    •  & Agostinho Carvalho
  • Article
    | Open Access

    Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.

    • Daehong Kim
    • , Giljun Park
    • , Jani Huuhtanen
    • , Sofie Lundgren
    • , Rajiv K. Khajuria
    • , Ana M. Hurtado
    • , Cecilia Muñoz-Calleja
    • , Laura Cardeñoso
    • , Valle Gómez-García de Soria
    • , Tzu Hua Chen-Liang
    • , Samuli Eldfors
    • , Pekka Ellonen
    • , Sari Hannula
    • , Matti Kankainen
    • , Oscar Bruck
    • , Anna Kreutzman
    • , Urpu Salmenniemi
    • , Tapio Lönnberg
    • , Andrés Jerez
    • , Maija Itälä-Remes
    • , Mikko Myllymäki
    • , Mikko A. I. Keränen
    •  & Satu Mustjoki
  • Article
    | Open Access

    In macrophages, IL-1β secretion is mediated by N-GSDMD pores in the plasma membrane (PM). Here the authors show that in neutrophils, IL-1β secretion occurs in the absence of PM pores, via autophagosomes; N-GSDMD does not traffic to PM but to azurophilic granules, thereby releasing neutrophil elastase which cleaves further N-GSDMD into alternative fragments.

    • Mausita Karmakar
    • , Martin Minns
    • , Elyse N. Greenberg
    • , Jose Diaz-Aponte
    • , Kersi Pestonjamasp
    • , Jennifer L. Johnson
    • , Joseph K. Rathkey
    • , Derek W. Abbott
    • , Kun Wang
    • , Feng Shao
    • , Sergio D. Catz
    • , George R. Dubyak
    •  & Eric Pearlman
  • Article
    | Open Access

    Immune infiltration provides critical information for health and disease, yet it is unclear what factors influence infiltration levels. Here, the authors analyze human tissue transcriptomes from the Genotype-Tissue Expression project to find infiltration patterns regulated by age, sex and host genetic information.

    • Andrew R. Marderstein
    • , Manik Uppal
    • , Akanksha Verma
    • , Bhavneet Bhinder
    • , Zakieh Tayyebi
    • , Jason Mezey
    • , Andrew G. Clark
    •  & Olivier Elemento
  • Article
    | Open Access

    Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells.

    • Beth Lucas
    • , Andrea J. White
    • , Emilie J. Cosway
    • , Sonia M. Parnell
    • , Kieran D. James
    • , Nick D. Jones
    • , Izumi Ohigashi
    • , Yousuke Takahama
    • , William E. Jenkinson
    •  & Graham Anderson
  • Article
    | Open Access

    RNA viruses can be detected by immune cell pattern recognition receptors, such as RLRs, resulting in MAVS-TBK1-IRF3 signalling and production of antiviral type 1 interferons. Here the authors show that macrophage TRAF3-interacting protein 3 regulates this signalling pathway by interacting with TRAF3 and TBK1 to suppress interferon responses.

    • Meng Deng
    • , Jason W. Tam
    • , Lufei Wang
    • , Kaixin Liang
    • , Sirui Li
    • , Lu Zhang
    • , Haitao Guo
    • , Xiaobo Luo
    • , Yang Zhang
    • , Alex Petrucelli
    • , Beckley K. Davis
    • , Brian J. Conti
    • , W. June Brickey
    • , Ching-Chang Ko
    • , Yu L. Lei
    • , Shaocong Sun
    •  & Jenny P. -Y. Ting
  • Article
    | Open Access

    Vaccines and targeted therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently lacking. Here, the authors report a human monoclonal antibody capable of neutralizing both authentic SARS-CoV and SARS-CoV-2 by targeting a common epitope.

    • Chunyan Wang
    • , Wentao Li
    • , Dubravka Drabek
    • , Nisreen M. A. Okba
    • , Rien van Haperen
    • , Albert D. M. E. Osterhaus
    • , Frank J. M. van Kuppeveld
    • , Bart L. Haagmans
    • , Frank Grosveld
    •  & Berend-Jan Bosch
  • Article
    | Open Access

    The gut microbiota has been reported to regulate the efficacy of cancer therapy. Here, the authors show that short-chain fatty acids, which are generated through bacterial fermentation, increases immune tolerance leading to resistance to anti-CTLA-4 immunotherapy in mice and patients with metastatic melanoma.

    • Clélia Coutzac
    • , Jean-Mehdi Jouniaux
    • , Angelo Paci
    • , Julien Schmidt
    • , Domenico Mallardo
    • , Atmane Seck
    • , Vahe Asvatourian
    • , Lydie Cassard
    • , Patrick Saulnier
    • , Ludovic Lacroix
    • , Paul-Louis Woerther
    • , Aurore Vozy
    • , Marie Naigeon
    • , Laetitia Nebot-Bral
    • , Mélanie Desbois
    • , Ester Simeone
    • , Christine Mateus
    • , Lisa Boselli
    • , Jonathan Grivel
    • , Emilie Soularue
    • , Patricia Lepage
    • , Franck Carbonnel
    • , Paolo Antonio Ascierto
    • , Caroline Robert
    •  & Nathalie Chaput
  • Article
    | Open Access

    PBRM1, encoding for a subunit of the SWI/SNF complex, is the second most frequently mutated gene in clear cell renal cell carcinoma (ccRCC). Here, the authors show that PBRM1 loss reduces IFNγ-mediated signalling resulting in a less immunogenic tumor microenvironment and that PBRM1 mutations correlate with lack of response to checkpoint inhibitor therapy in ccRCC patients..

    • Xian-De Liu
    • , Wen Kong
    • , Christine B. Peterson
    • , Daniel J. McGrail
    • , Anh Hoang
    • , Xuesong Zhang
    • , Truong Lam
    • , Patrick G. Pilie
    • , Haifeng Zhu
    • , Kathryn E. Beckermann
    • , Scott M. Haake
    • , Sevinj Isgandrova
    • , Margarita Martinez-Moczygemba
    • , Nidhi Sahni
    • , Nizar M. Tannir
    • , Shiaw-Yih Lin
    • , W. Kimryn Rathmell
    •  & Eric Jonasch
  • Article
    | Open Access

    Classical human dendritic cells (cDCs) are rare sentinel cells specialized in regulating adaptive immunity. Here, the authors show that expression of membrane bound FLT3L, along with stem cell factor (SCF) and CXCL12 in stromal cells induces specification of pre/AS-DCs, type 1 and type2 cDC from haematopoietic stem cells.

    • Giorgio Anselmi
    • , Kristine Vaivode
    • , Charles-Antoine Dutertre
    • , Pierre Bourdely
    • , Yoann Missolo-Koussou
    • , Evan Newell
    • , Oliver Hickman
    • , Kristie Wood
    • , Alka Saxena
    • , Julie Helft
    • , Florent Ginhoux
    •  & Pierre Guermonprez
  • Article
    | Open Access

    Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Anna Rao
    • , Otto Strauss
    • , Efthymia Kokkinou
    • , Mélanie Bruchard
    • , Kumar P. Tripathi
    • , Heinrich Schlums
    • , Anna Carrasco
    • , Luca Mazzurana
    • , Viktoria Konya
    • , Eduardo J. Villablanca
    • , Niklas K. Björkström
    • , Ulrik Lindforss
    • , Hergen Spits
    •  & Jenny Mjösberg
  • Article
    | Open Access

    Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of “swarms”. Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells.

    • Alex Hopke
    • , Allison Scherer
    • , Samantha Kreuzburg
    • , Michael S. Abers
    • , Christa S. Zerbe
    • , Mary C. Dinauer
    • , Michael K. Mansour
    •  & Daniel Irimia
  • Article
    | Open Access

    Regulating polyadenylation is important for mRNA stability, which can in turn affect B cell maturation and humoral immune responses. Here the authors use Nanopore poly(A) sequencing to explore the importance of the cytoplasmic poly(A) polymerase TENT5C, particularly in the production of immunoglobulins.

    • Aleksandra Bilska
    • , Monika Kusio-Kobiałka
    • , Paweł S. Krawczyk
    • , Olga Gewartowska
    • , Bartosz Tarkowski
    • , Kamil Kobyłecki
    • , Dominika Nowis
    • , Jakub Golab
    • , Jakub Gruchota
    • , Ewa Borsuk
    • , Andrzej Dziembowski
    •  & Seweryn Mroczek
  • Article
    | Open Access

    Virulent pathogens generally induce a stronger mucosal immunity than avirulent strains, but whether the associated inflammation is necessary for this is unclear. Here, using auxotrophic Salmonella enterica, the authors show that virulence factor function determines induction of protective IgA.

    • Simona P. Pfister
    • , Olivier P. Schären
    • , Luca Beldi
    • , Andrea Printz
    • , Matheus D. Notter
    • , Mohana Mukherjee
    • , Hai Li
    • , Julien P. Limenitakis
    • , Joel P. Werren
    • , Disha Tandon
    • , Miguelangel Cuenca
    • , Stefanie Hagemann
    • , Stephanie S. Uster
    • , Miguel A. Terrazos
    • , Mercedes Gomez de Agüero
    • , Christian M. Schürch
    • , Fernanda M. Coelho
    • , Roy Curtiss III
    • , Emma Slack
    • , Maria L. Balmer
    •  & Siegfried Hapfelmeier
  • Article
    | Open Access

    Moderate consumption of alcohol is associated with protection from some autoimmune diseases. Here the authors show that ethanol and its metabolite acetate can protect mice from collagen-induced arthritis and provide evidence that the mechanism of this effect might be via inhibition of the effector function of T follicular helper cells.

    • Vugar Azizov
    • , Katharina Dietel
    • , Franziska Steffen
    • , Kerstin Dürholz
    • , Julia Meidenbauer
    • , Sébastien Lucas
    • , Michael Frech
    • , Yasunori Omata
    • , Narges Tajik
    • , Lisa Knipfer
    • , Anne Kolenbrander
    • , Silvia Seubert
    • , Dennis Lapuente
    • , Maria V. Sokolova
    • , Jörg Hofmann
    • , Matthias Tenbusch
    • , Andreas Ramming
    • , Ulrike Steffen
    • , Falk Nimmerjahn
    • , Ralf Linker
    • , Stefan Wirtz
    • , Martin Herrmann
    • , Vladimir Temchura
    • , Kerstin Sarter
    • , Georg Schett
    •  & Mario M. Zaiss
  • Article
    | Open Access

    Intestinal dysbiosis is associated with an ever-growing list of autoimmune diseases. Here the authors show that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.

    • Narges Tajik
    • , Michael Frech
    • , Oscar Schulz
    • , Fabian Schälter
    • , Sébastien Lucas
    • , Vugar Azizov
    • , Kerstin Dürholz
    • , Franziska Steffen
    • , Yasunori Omata
    • , Andreas Rings
    • , Marko Bertog
    • , Aroldo Rizzo
    • , Aida Iljazovic
    • , Marijana Basic
    • , Arnd Kleyer
    • , Stephan Culemann
    • , Gerhard Krönke
    • , Yubin Luo
    • , Klaus Überla
    • , Udo S. Gaipl
    • , Benjamin Frey
    • , Till Strowig
    • , Kerstin Sarter
    • , Stephan C. Bischoff
    • , Stefan Wirtz
    • , Juan D. Cañete
    • , Francesco Ciccia
    • , Georg Schett
    •  & Mario M. Zaiss
  • 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 molecular mechanisms that drive irreversible acute liver failure remain poorly characterized. Here, the authors show that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage during acute liver injury by blocking restorative neutrophil driven inflammation.

    • Abhishek Chauhan
    • , Lozan Sheriff
    • , Mohammed T. Hussain
    • , Gwilym J. Webb
    • , Daniel A. Patten
    • , Emma L. Shepherd
    • , Robert Shaw
    • , Christopher J. Weston
    • , Debashis Haldar
    • , Samuel Bourke
    • , Rajan Bhandari
    • , Stephanie Watson
    • , David H. Adams
    • , Steve P. Watson
    •  & Patricia F. Lalor
  • Article
    | Open Access

    Helminth infections are associated with a reduction in inflammatory pathology in rodent models of type 1 diabetes. Here, the authors show patient data and that trehalose (produced by H. polygyrus) can alter the microbiome of mice, inducing regulatory CD8+ T cells and reducing susceptibility to autoimmune diabetes.

    • Chikako Shimokawa
    • , Tamotsu Kato
    • , Tadashi Takeuchi
    • , Noriyasu Ohshima
    • , Takao Furuki
    • , Yoshiaki Ohtsu
    • , Kazutomo Suzue
    • , Takashi Imai
    • , Seiji Obi
    • , Alex Olia
    • , Takashi Izumi
    • , Minoru Sakurai
    • , Hirokazu Arakawa
    • , Hiroshi Ohno
    •  & Hajime Hisaeda
  • Article
    | Open Access

    TAGAP gene variants are linked to human autoimmunity. Here the authors identify TAGAP as a Dectin-1 and EphB2-binding protein mediating antifungal innate immune signaling and cytokine production, and demonstrate TAGAP in non-T cells promotes Th17 response in mouse models of infection and autoimmunity.

    • Jianwen Chen
    • , Ruirui He
    • , Wanwei Sun
    • , Ru Gao
    • , Qianwen Peng
    • , Liwen Zhu
    • , Yanyun Du
    • , Xiaojian Ma
    • , Xiaoli Guo
    • , Huazhi Zhang
    • , Chengcheng Tan
    • , Junhan Wang
    • , Wei Zhang
    • , Xiufang Weng
    • , Jianghong Man
    • , Hermann Bauer
    • , Qing K. Wang
    • , Bradley N. Martin
    • , Cun-Jin Zhang
    • , Xiaoxia Li
    •  & Chenhui Wang
  • Article
    | Open Access

    Peptide-MHC (pMHC) tetramers are important tools for probing T cell repertoire and adaptive immune responses. Here the authors use a molecular chaperone, TAPBPR, to develop a high-throughput, multiplexible platform for pMHC tetramer generation to facilitate simultaneous assessments of T cell repertoire/antigen specificity and transcriptome.

    • Sarah A. Overall
    • , Jugmohit S. Toor
    • , Stephanie Hao
    • , Mark Yarmarkovich
    • , Sara M. O’Rourke
    • , Giora I. Morozov
    • , Son Nguyen
    • , Alberto Sada Japp
    • , Nicolas Gonzalez
    • , Danai Moschidi
    • , Michael R. Betts
    • , John M. Maris
    • , Peter Smibert
    •  & Nikolaos G. Sgourakis
  • Article
    | Open Access

    α-Synuclein-specific T cell reactivity is preferentially associated with Parkinson’s disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that α-syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.

    • Cecilia S. Lindestam Arlehamn
    • , Rekha Dhanwani
    • , John Pham
    • , Rebecca Kuan
    • , April Frazier
    • , Juliana Rezende Dutra
    • , Elizabeth Phillips
    • , Simon Mallal
    • , Mario Roederer
    • , Karen S. Marder
    • , Amy W. Amara
    • , David G. Standaert
    • , Jennifer G. Goldman
    • , Irene Litvan
    • , Bjoern Peters
    • , David Sulzer
    •  & Alessandro Sette
  • Article
    | Open Access

    Asthma is a common disease of the airways for which numerous genetic loci have been identified. Here, Han et al. carry out a genome-wide analysis for asthma to identify additional loci, report sex-stratified and genetic risk score analyses, and functionally follow-up one locus using a murine model of airway hyperreactivity.

    • Yi Han
    • , Qiong Jia
    • , Pedram Shafiei Jahani
    • , Benjamin P. Hurrell
    • , Calvin Pan
    • , Pin Huang
    • , Janet Gukasyan
    • , Nicholas C. Woodward
    • , Eleazar Eskin
    • , Frank D. Gilliland
    • , Omid Akbari
    • , Jaana A. Hartiala
    •  & Hooman Allayee
  • Article
    | Open Access

    Group 3 innate lymphoid cells (ILC3s) promote T cell activation in the spleen but suppress it in the gut. Here, the authors show that this distinct regulation is mediated by gut microbiota-induced IL-23 and IFN-γ, respectively, and, along with the article by Rao et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Frank Michael Lehmann
    • , Nicole von Burg
    • , Robert Ivanek
    • , Claudia Teufel
    • , Edit Horvath
    • , Annick Peter
    • , Gleb Turchinovich
    • , Daniel Staehli
    • , Tobias Eichlisberger
    • , Mercedes Gomez de Agüero
    • , Mairene Coto-Llerena
    • , Michaela Prchal-Murphy
    • , Veronika Sexl
    • , Mohamed Bentires-Alj
    • , Christoph Mueller
    •  & Daniela Finke
  • Article
    | Open Access

    Cytokines critically control the differentiation and functions of activated naïve and memory T cells. Here the authors show, using multi-omics and single-cell analyses, that naïve and memory T cells exhibit distinct cytokine responses, in which an ‘effectorness gradient’ is depicted by a transcriptional continuum, which shapes the downstream genetic programs.

    • Eddie Cano-Gamez
    • , Blagoje Soskic
    • , Theodoros I. Roumeliotis
    • , Ernest So
    • , Deborah J. Smyth
    • , Marta Baldrighi
    • , David Willé
    • , Nikolina Nakic
    • , Jorge Esparza-Gordillo
    • , Christopher G. C. Larminie
    • , Paola G. Bronson
    • , David F. Tough
    • , Wendy C. Rowan
    • , Jyoti S. Choudhary
    •  & Gosia Trynka
  • Article
    | Open Access

    Sex differences in the immune response to vaccines and infections have been well described in children and adults. Here the authors describe, in a cohort of 177 HIV-infected infants, innate immune sex differences in fetal life that increase female susceptibility to intrauterine HIV infection and increase the chances of subsequent HIV remission in infected males.

    • Emily Adland
    • , Jane Millar
    • , Nomonde Bengu
    • , Maximilian Muenchhoff
    • , Rowena Fillis
    • , Kenneth Sprenger
    • , Vuyokasi Ntlantsana
    • , Julia Roider
    • , Vinicius Vieira
    • , Katya Govender
    • , John Adamson
    • , Nelisiwe Nxele
    • , Christina Ochsenbauer
    • , John Kappes
    • , Luisa Mori
    • , Jeroen van Lobenstein
    • , Yeney Graza
    • , Kogielambal Chinniah
    • , Constant Kapongo
    • , Roopesh Bhoola
    • , Malini Krishna
    • , Philippa C. Matthews
    • , Ruth Penya Poderos
    • , Marta Colomer Lluch
    • , Maria C. Puertas
    • , Julia G. Prado
    • , Neil McKerrow
    • , Moherndran Archary
    • , Thumbi Ndung’u
    • , Andreas Groll
    • , Pieter Jooste
    • , Javier Martinez-Picado
    • , Marcus Altfeld
    •  & Philip Goulder
  • Article
    | Open Access

    Immunotherapy has tremendous potential to treat many patients with cancer. In this study, the authors investigate the impact of gender on the response to therapy, highlighting the importance to include omics profiling in clinical studies.

    • Youqiong Ye
    • , Ying Jing
    • , Liang Li
    • , Gordon B. Mills
    • , Lixia Diao
    • , Hong Liu
    •  & Leng Han
  • Article
    | Open Access

    It is unclear how microbial-induced inflammation promotes neoplastic transformation in colitis-associated cancer (CAC). Here, the authors use models of CAC to show that inflammation induces 8-oxoguanine lesions in DNA, and that antioxidants can reduce these DNA lesions as well as CAC.

    • Thergiory Irrazabal
    • , Bhupesh K. Thakur
    • , Mingsong Kang
    • , Yann Malaise
    • , Catherine Streutker
    • , Erin O. Y. Wong
    • , Julia Copeland
    • , Robert Gryfe
    • , David S. Guttman
    • , William W. Navarre
    •  & Alberto Martin