Immunology

  • Article | | open

    SIRPa is most commonly known as a phagocytosis inhibitory receptor expressed by myeloid cells. Here the authors show SIRPa is expressed on a subset of CD8+ T cells with higher proliferative and effector activity during the chronic phase of the immune response to viral infection.

    • Lara M. Myers
    • , Michal Caspi Tal
    • , Laughing Bear Torrez Dulgeroff
    • , Aaron B. Carmody
    • , Ronald J. Messer
    • , Gunsagar Gulati
    • , Ying Ying Yiu
    • , Matthew M. Staron
    • , Cesar Lopez Angel
    • , Rahul Sinha
    • , Maxim Markovic
    • , Edward A. Pham
    • , Benjamin Fram
    • , Aijaz Ahmed
    • , Aaron M. Newman
    • , Jeffrey S. Glenn
    • , Mark M. Davis
    • , Susan M. Kaech
    • , Irving L. Weissman
    •  & Kim J. Hasenkrug
  • Article | | open

    Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are still unclear. Here the authors show that a SCFA, pentanoate, suppresses autoimmune inflammation in mouse models of colitis and multiple sclerosis via epigenetic modulation of immune cell metabolic and functional pathways.

    • Maik Luu
    • , Sabine Pautz
    • , Vanessa Kohl
    • , Rajeev Singh
    • , Rossana Romero
    • , Sébastien Lucas
    • , Jörg Hofmann
    • , Hartmann Raifer
    • , Niyati Vachharajani
    • , Lucia Campos Carrascosa
    • , Boris Lamp
    • , Andrea Nist
    • , Thorsten Stiewe
    • , Yoav Shaul
    • , Till Adhikary
    • , Mario M. Zaiss
    • , Matthias Lauth
    • , Ulrich Steinhoff
    •  & Alexander Visekruna
  • Article | | open

    Infection of a cell with influenza B virus (IBV) often results in cell death and the role of surviving cells in pathogenesis is unclear. Here, Dumm et al. generate a recombinant IBV that activates a host-cell reporter to permanently label infected cells, and show that surviving cells are important to preserve epithelial barrier function.

    • Rebekah E. Dumm
    • , Jessica K. Fiege
    • , Barbara M. Waring
    • , Chay T. Kuo
    • , Ryan A. Langlois
    •  & Nicholas S. Heaton
  • Article | | open

    The fusion peptide (FP) of HIV envelope (Env) is critical in the cell entry process. Here, Kumar et al. present crystal structures of B41 SOSIP.664 Env trimer and show the dynamic nature of the FP and proximal region, which likely relates to conformational rearrangements required for membrane fusion.

    • Sonu Kumar
    • , Anita Sarkar
    • , Pavel Pugach
    • , Rogier W. Sanders
    • , John P. Moore
    • , Andrew B. Ward
    •  & Ian A. Wilson
  • Article | | open

    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

    Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

    • Ping Wang
    • , Jing Geng
    • , Jiahui Gao
    • , Hao Zhao
    • , Junhong Li
    • , Yiran Shi
    • , Bingying Yang
    • , Chen Xiao
    • , Yueyue Linghu
    • , Xiufeng Sun
    • , Xin Chen
    • , Lixin Hong
    • , Funiu Qin
    • , Xun Li
    • , Jau-Song Yu
    • , Han You
    • , Zengqiang Yuan
    • , Dawang Zhou
    • , Randy L. Johnson
    •  & Lanfen Chen
  • Article | | open

    Adenovirus based (AdV) vectors are promising platforms for therapeutics and vaccines, but receptor usage of serotypes in clinical development remains unclear. Here, based on crystal structures and modeling, Baker et al. show that HAdV-D26/48 fiber knob protein interacts weakly with CAR but not with CD46 or DSG2.

    • Alexander T. Baker
    • , Alexander Greenshields-Watson
    • , Lynda Coughlan
    • , James A. Davies
    • , Hanni Uusi-Kerttula
    • , David K. Cole
    • , Pierre J. Rizkallah
    •  & Alan L. Parker
  • Article | | open

    How HIV reservoirs are shaped over time on antiviral therapy is poorly understood. Here, the authors analyze the dynamics of the HIV reservoir by longitudinal proviral sequencing revealing that HIV reservoir expression can contribute to its clearance and paradoxically even to its persistence.

    • Marilia Rita Pinzone
    • , D. Jake VanBelzen
    • , Sam Weissman
    • , Maria Paola Bertuccio
    • , LaMont Cannon
    • , Emmanuele Venanzi-Rullo
    • , Stephen Migueles
    • , R. Brad Jones
    • , Talia Mota
    • , Sarah B. Joseph
    • , Kevin Groen
    • , Alexander O. Pasternak
    • , Wei-Ting Hwang
    • , Brad Sherman
    • , Anastasios Vourekas
    • , Giuseppe Nunnari
    •  & Una O’Doherty
  • Article | | open

    Quaternary contacts mediated by an extended heavy-chain framework region 3 (FR3) have been shown to improve binding to HIV envelope and virus neutralization for a few antibodies. Here, Liu et al. engraft such an FR3 loop onto several potent broadly neutralizing antibodies, resulting in improved neutralization activity and pharmacokinetics.

    • Qingbo Liu
    • , Yen-Ting Lai
    • , Peng Zhang
    • , Mark K. Louder
    • , Amarendra Pegu
    • , Reda Rawi
    • , Mangaiarkarasi Asokan
    • , Xuejun Chen
    • , Chen-Hsiang Shen
    • , Gwo-Yu Chuang
    • , Eun Sung Yang
    • , Huiyi Miao
    • , Yuge Wang
    • , Anthony S. Fauci
    • , Peter D. Kwong
    • , John R. Mascola
    •  & Paolo Lusso
  • Article | | open

    Type-2 innate lymphoid cells (ILC2s) are an immune population secreting Th2 cytokines playing a role in the regulation of adipose metabolic homeostasis. Here the authors show that engagement of GITR, a member of the TNF superfamily, in activated ILC2s is protective against insulin resistance in both a preventive and a therapeutic manner in the context of obesity.

    • Lauriane Galle-Treger
    • , Ishwarya Sankaranarayanan
    • , Benjamin P. Hurrell
    • , Emily Howard
    • , Richard Lo
    • , Hadi Maazi
    • , Gavin Lewis
    • , Homayon Banie
    • , Alan L. Epstein
    • , Peisheng Hu
    • , Virender K. Rehan
    • , Frank D. Gilliland
    • , Hooman Allayee
    • , Pejman Soroosh
    • , Arlene H. Sharpe
    •  & Omid Akbari
  • Article | | open

    T cells express specific T cell receptors (TCR) to recognise antigens and initiate adaptive immune responses. Here the authors show, in a mouse model of autoimmune encephalomyelitis, that memory-like CD4 T cells expressing unrelated TCR can also infiltrate the spinal cord and contribute to autoimmunity.

    • Hong-Gyun Lee
    • , Jae-Ung Lee
    • , Do-Hyun Kim
    • , Sangho Lim
    • , Insoo Kang
    •  & Je-Min Choi
  • Article | | open

    Ubiquitination may control protein stability or function. Here the authors show that an ubiquitination enzyme, Hectd3, ubiquitinates Stat3 and Malt1 to modulate their function but not degradation in T cells, and thereby promoting the differentiation of pathogenic Th17 cells and susceptibility to a mouse model of multiple sclerosis.

    • Jonathan J. Cho
    • , Zhiwei Xu
    • , Upasana Parthasarathy
    • , Theodore T. Drashansky
    • , Eric Y. Helm
    • , Ashley N. Zuniga
    • , Kyle J. Lorentsen
    • , Samira Mansouri
    • , Joshua Y. Cho
    • , Mariola J. Edelmann
    • , Duc M. Duong
    • , Torben Gehring
    • , Thomas Seeholzer
    • , Daniel Krappmann
    • , Mohammad N. Uddin
    • , Danielle Califano
    • , Rejean L. Wang
    • , Lei Jin
    • , Hongmin Li
    • , Dongwen Lv
    • , Daohong Zhou
    • , Liang Zhou
    •  & Dorina Avram
  • Article | | open

    Programmed cell death regulates early development but how various factors (for example, TRADD, FADD and RIPKs) regulate this is unclear. Here, the authors show that a single allele of Tradd is essential for survival, when both Ripk3 and Ripk1 are knocked out in mice, and RIPK1 protects thymocytes from TNF-induced apoptosis.

    • John P. Dowling
    • , Mohamed Alsabbagh
    • , Christina Del Casale
    • , Zheng-Gang Liu
    •  & Jianke Zhang
  • Article | | open

    There has been a lack of multi-year landscape-scale studies on the effect of neonicotinoids on honeybee health. Here, Osterman et al. show that clothianidin exposure via seed-treated rapeseed has no negative impact on honeybee colony development, microbial pathogens/symbionts or immune gene expression.

    • Julia Osterman
    • , Dimitry Wintermantel
    • , Barbara Locke
    • , Ove Jonsson
    • , Emilia Semberg
    • , Piero Onorati
    • , Eva Forsgren
    • , Peter Rosenkranz
    • , Thorsten Rahbek-Pedersen
    • , Riccardo Bommarco
    • , Henrik G. Smith
    • , Maj Rundlöf
    •  & Joachim R. de Miranda
  • Article | | open

    How Japanese encephalitis virus (JEV) penetrates the blood-brain barrier (BBB) remains unclear. Here, using a genetic mouse model and a virulent JEV strain, the authors show that perivascular mast cells (MC) mediate JEV neuroinvasion and identify the MC-protease chymase as a potential therapeutic target.

    • Justin T. Hsieh
    • , Abhay P. S. Rathore
    • , Gayathri Soundarajan
    •  & Ashley L. St. John
  • Article | | open

    Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

    • Maria Gutierrez-Arcelus
    • , Nikola Teslovich
    • , Alex R. Mola
    • , Rafael B. Polidoro
    • , Aparna Nathan
    • , Hyun Kim
    • , Susan Hannes
    • , Kamil Slowikowski
    • , Gerald F. M. Watts
    • , Ilya Korsunsky
    • , Michael B. Brenner
    • , Soumya Raychaudhuri
    •  & Patrick J. Brennan
  • Article | | open

    Microfold cells (M-cell) are specialized cells of the intestine that sample luminal microbiota and dietary antigens. Here the authors show that epithelial non-canonical NFκB signalling, as induced by NIK, is important for M-cells maintenance, yet constitutive NIK activation is associated with gut inflammation and inflammatory bowel disease.

    • Sadeesh K. Ramakrishnan
    • , Huabing Zhang
    • , Xiaoya Ma
    • , Inkyung Jung
    • , Andrew J. Schwartz
    • , Daniel Triner
    • , Samantha N. Devenport
    • , Nupur K. Das
    • , Xiang Xue
    • , Melody Y. Zeng
    • , Yinling Hu
    • , Richard M. Mortensen
    • , Joel K Greenson
    • , Marilia Cascalho
    • , Christiane E. Wobus
    • , Justin A. Colacino
    • , Gabriel Nunez
    • , Liangyou Rui
    •  & Yatrik M. Shah
  • Article | | open

    Corticosteroids are host-directed drugs that enhance survival of tuberculosis patients through unclear mechanisms. Here, Gräb et al. show that corticosteroids inhibit necrotic death of cells infected with Mycobacterium tuberculosis by facilitating MKP-1-dependent dephosphorylation of p38 MAPK.

    • Jessica Gräb
    • , Isabelle Suárez
    • , Edeltraud van Gumpel
    • , Sandra Winter
    • , Fynn Schreiber
    • , Anna Esser
    • , Christoph Hölscher
    • , Melanie Fritsch
    • , Marc Herb
    • , Michael Schramm
    • , Laurens Wachsmuth
    • , Christian Pallasch
    • , Manolis Pasparakis
    • , Hamid Kashkar
    •  & Jan Rybniker
  • Article | | open

    Somatic mutations within antibody framework regions (FWR) can alter structural flexibility, but their role in maturation of broadly neutralizing antibodies (bnAbs) is unclear. Here the authors show how FWR mutations impact interdomain conformational flexibility and paratope plasticity during bnAb development.

    • Rory Henderson
    • , Brian E. Watts
    • , Hieu N. Ergin
    • , Kara Anasti
    • , Robert Parks
    • , Shi-Mao Xia
    • , Ashley Trama
    • , Hua-Xin Liao
    • , Kevin O. Saunders
    • , Mattia Bonsignori
    • , Kevin Wiehe
    • , Barton F. Haynes
    •  & S. Munir Alam
  • Article | | open

    High-throughput sequencing and analyzes of antibody repertoire provide important information on immune responses, but current methodologies are limited in sequence assembly precision and haplotype inference validity. Here the authors propose a new Bayesian haplotyping method, and attest its broad application with a large, multi-individual dataset.

    • Moriah Gidoni
    • , Omri Snir
    • , Ayelet Peres
    • , Pazit Polak
    • , Ida Lindeman
    • , Ivana Mikocziova
    • , Vikas Kumar Sarna
    • , Knut E. A. Lundin
    • , Christopher Clouser
    • , Francois Vigneault
    • , Andrew M. Collins
    • , Ludvig M. Sollid
    •  & Gur Yaari
  • Article | | open

    Diverse interactions between the nervous and immune systems have been shown, but specific mechanistic insights are still lacking. Here the authors show, using both mouse inflammation models and clinical correlation, that adrenergic nerve may ameliorate inflammation by inducing repulsive guidance molecule A signalling.

    • Andreas Körner
    • , Martin Schlegel
    • , Torsten Kaussen
    • , Verena Gudernatsch
    • , Georg Hansmann
    • , Timo Schumacher
    • , Martin Giera
    •  & Valbona Mirakaj
  • Article | | open

    Elevated MYC levels can sensitize tumor cells to apoptosis. In this study, the authors demonstrate that AMPK activation and BCL-2/BCL-XL inhibition have a synergistic effect on apoptosis, and that together with anti PD-1 therapy they can suppress Myc-driven mammary tumor growth.

    • Heidi M. Haikala
    • , Johanna M. Anttila
    • , Elsa Marques
    • , Tiina Raatikainen
    • , Mette Ilander
    • , Henna Hakanen
    • , Hanna Ala-Hongisto
    • , Mariel Savelius
    • , Diego Balboa
    • , Bjoern Von Eyss
    • , Vilja Eskelinen
    • , Pauliina Munne
    • , Anni I. Nieminen
    • , Timo Otonkoski
    • , Julia Schüler
    • , Teemu D. Laajala
    • , Tero Aittokallio
    • , Harri Sihto
    • , Johanna Mattson
    • , Päivi Heikkilä
    • , Marjut Leidenius
    • , Heikki Joensuu
    • , Satu Mustjoki
    • , Panu Kovanen
    • , Martin Eilers
    • , Joel D. Leverson
    •  & Juha Klefström
  • Article | | open

    Hematopoietic stem cell (HSC) transplantation is a desirable treatment for many non-malignant and malignant diseases, but its use requires preconditioning of recipients with irradiation or chemotherapy that often induces high toxicity. Here the authors show that antibody-drug-conjugate to CD117, a HSC marker, allows specific and efficient preconditioning for HSC therapy.

    • Agnieszka Czechowicz
    • , Rahul Palchaudhuri
    • , Amelia Scheck
    • , Yu Hu
    • , Jonathan Hoggatt
    • , Borja Saez
    • , Wendy W. Pang
    • , Michael K. Mansour
    • , Tiffany A. Tate
    • , Yan Yi Chan
    • , Emily Walck
    • , Gerlinde Wernig
    • , Judith A. Shizuru
    • , Florian Winau
    • , David T. Scadden
    •  & Derrick J. Rossi
  • Article | | open

    Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.

    • Zhanzhuo Li
    • , Agnieszka Czechowicz
    • , Amelia Scheck
    • , Derrick J. Rossi
    •  & Philip M. Murphy
  • Article | | open

    Host genetics modulates gut microbiota composition, which in turn affects host health, but little is known about the specific genes involved. Here, Berg et al. show that TGFβ/BMP immune signalling affects abundance and function of commensal Enterobacter species in C. elegans.

    • Maureen Berg
    • , David Monnin
    • , Juhyun Cho
    • , Lydia Nelson
    • , Alex Crits-Christoph
    •  & Michael Shapira
  • Article | | open

    Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.

    • Linda Reiling
    • , Michelle J. Boyle
    • , Michael T. White
    • , Danny W. Wilson
    • , Gaoqian Feng
    • , Rupert Weaver
    • , D. Herbert Opi
    • , Kristina E. M. Persson
    • , Jack S. Richards
    • , Peter M. Siba
    • , Freya J. I. Fowkes
    • , Eizo Takashima
    • , Takafumi Tsuboi
    • , Ivo Mueller
    •  & James G. Beeson
  • Article | | open

    The immunosuppressive tumor environment and the lack of functional anti-tumor immunity are major limiting factors in immunotherapy. Here the authors show that human and mouse tumors are infiltrated by virus-specific memory T cells, which can be harnessed by viral peptides to induce local and systemic anti-tumor immunity and synergize with checkpoint blockade.

    • Pamela C. Rosato
    • , Sathi Wijeyesinghe
    • , J. Michael Stolley
    • , Christine E. Nelson
    • , Rachel L. Davis
    • , Luke S. Manlove
    • , Christopher A. Pennell
    • , Bruce R. Blazar
    • , Clark C. Chen
    • , Melissa A. Geller
    • , Vaiva Vezys
    •  & David Masopust
  • Article | | open

    A chromatin remodelling factor Satb1 is essential for T cell lineage development in the thymus. Here the authors show that while Satb1 is dispensable for the differentiation of Th17 cells and their response to gut commensals, it plays a critical role in pathogenic Th17 effector function in EAE by directly activating Bhlhe40 and modulating PD-1.

    • Keiko Yasuda
    • , Yohko Kitagawa
    • , Ryoji Kawakami
    • , Yoshitaka Isaka
    • , Hitomi Watanabe
    • , Gen Kondoh
    • , Terumi Kohwi-Shigematsu
    • , Shimon Sakaguchi
    •  & Keiji Hirota
  • Article | | open

    CD47 is a promising new target in cancer immunotherapy and recently the pro-phagocytic signal SLAMF7 has been shown to have a crucial role in phagocytosis induced by CD47-blocking antibody in hematological tumors. In this study, the authors demonstrate that SLAMF7 expressed by cancer cells is not required for phagocytosis suggesting that, in contrast to CD47 expression, SLAMF7 should not be used as selection criterion for CD47-targeted therapy.

    • Yuan He
    • , Renee Bouwstra
    • , Valerie R. Wiersma
    • , Mathilde de Jong
    • , Harm Jan Lourens
    • , Rudolf Fehrmann
    • , Marco de Bruyn
    • , Emanuele Ammatuna
    • , Gerwin Huls
    • , Tom van Meerten
    •  & Edwin Bremer
  • Article | | open

    High fat diets (HFD) are thought to perturb murine hematopoiesis as a result of obesity. Here the authors find that short-term HFD reduces hematopoietic stem cells (HSC), disrupts lipid rafts and TGF-β1 signalling. Injecting HFD-fed mice with recombinant TGF-β1 can rescue HSC loss.

    • François Hermetet
    • , Anne Buffière
    • , Aziza Aznague
    • , Jean-Paul Pais de Barros
    • , Jean-Noël Bastie
    • , Laurent Delva
    •  & Ronan Quéré
  • Article | | open

    Natural killer (NK) cells are functionally calibrated against self MHC during a process termed education. Here the authors show that NK cell education is associated with the accumulation of dense-core secretory lysosomes for expedited release of granzyme B and Ca2+ flux upon target recognition and NK cell activation.

    • Jodie P. Goodridge
    • , Benedikt Jacobs
    • , Michelle L. Saetersmoen
    • , Dennis Clement
    • , Quirin Hammer
    • , Trevor Clancy
    • , Ellen Skarpen
    • , Andreas Brech
    • , Johannes Landskron
    • , Christian Grimm
    • , Aline Pfefferle
    • , Leonardo Meza-Zepeda
    • , Susanne Lorenz
    • , Merete Thune Wiiger
    • , William E. Louch
    • , Eivind Heggernes Ask
    • , Lisa L. Liu
    • , Vincent Yi Sheng Oei
    • , Una Kjällquist
    • , Sten Linnarsson
    • , Sandip Patel
    • , Kjetil Taskén
    • , Harald Stenmark
    •  & Karl-Johan Malmberg
  • Article | | open

    The role of microglia following spinal cord injury is not fully understood. Here, using transgenic approaches to selectively label microglia and not macrophages in mice, the authors show that microglia are highly active and accumulate at the edge of the lesion in the first weeks post injury, and also that inhibiting microglia activation impairs recovery in the early stages after spinal cord injury.

    • Victor Bellver-Landete
    • , Floriane Bretheau
    • , Benoit Mailhot
    • , Nicolas Vallières
    • , Martine Lessard
    • , Marie-Eve Janelle
    • , Nathalie Vernoux
    • , Marie-Ève Tremblay
    • , Tobias Fuehrmann
    • , Molly S. Shoichet
    •  & Steve Lacroix
  • Article | | open

    Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.

    • Gregory M. LaMonte
    • , Pamela Orjuela-Sanchez
    • , Jaeson Calla
    • , Lawrence T. Wang
    • , Shangzhong Li
    • , Justine Swann
    • , Annie N. Cowell
    • , Bing Yu Zou
    • , Alyaa M. Abdel-Haleem Mohamed
    • , Zaira Hellen Villa Galarce
    • , Marta Moreno
    • , Carlos Tong Rios
    • , Joseph M. Vinetz
    • , Nathan Lewis
    •  & Elizabeth A. Winzeler
  • Article | | open

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    • , Jack A Bibby
    • , Wing Wu
    • , Klaus Stensgaard Frederiksen
    • , Ceri A. Roberts
    • , Zoe Hall
    • , Gaelle LeFriec
    • , Kevin A. Robertson
    • , Paul Lavender
    • , Jens Gammeltoft Gerwien
    • , Leonie S. Taams
    • , Julian L. Griffin
    • , Emanuele de Rinaldis
    • , Lisa G. M. van Baarsen
    • , Claudia Kemper
    • , Peter Ghazal
    •  & Andrew P. Cope
  • Article | | open

    Seasonal malaria chemoprevention provides substantial benefit for young children, but resistance to used drugs will likely develop. Here, Chotsiri et al. evaluate the use of dihydroartemisinin-piperaquine as a regimen in 179 children, and population-based simulations suggest that small children would benefit from a higher and extended dosage.

    • Palang Chotsiri
    • , Issaka Zongo
    • , Paul Milligan
    • , Yves Daniel Compaore
    • , Anyirékun Fabrice Somé
    • , Daniel Chandramohan
    • , Warunee Hanpithakpong
    • , François Nosten
    • , Brian Greenwood
    • , Philip J. Rosenthal
    • , Nicholas J. White
    • , Jean-Bosco Ouédraogo
    •  & Joel Tarning
  • Article | | open

    Organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), are not offered for transplantation due to a high risk of transmission. Here, Galasso et al. develop a method for treatment of HCV-infected human donor lungs that is safe and prevents HCV transmission in the pig model.

    • Marcos Galasso
    • , Jordan J. Feld
    • , Yui Watanabe
    • , Mauricio Pipkin
    • , Cara Summers
    • , Aadil Ali
    • , Robert Qaqish
    • , Manyin Chen
    • , Rafaela V. P. Ribeiro
    • , Khaled Ramadan
    • , Layla Pires
    • , Vanderlei S. Bagnato
    • , Cristina Kurachi
    • , Vera Cherepanov
    • , Gray Moonen
    • , Anajara Gazzalle
    • , Thomas K. Waddell
    • , Mingyao Liu
    • , Shaf Keshavjee
    • , Brian C. Wilson
    • , Atul Humar
    •  & Marcelo Cypel
  • Article | | open

    Blocking the PD-1 pathway was shown to be effective in amyloid beta mouse models, yet little is known about its therapeutic potential in models of tauopathy. The authors show here that blocking PD-L1, a PD-1 ligand, is similarly effective, and that both treatments reversed cognitive deficiencies, and modified disease pathology not only in an animal model of AD, but also in the DM-hTAU mouse tauopathy model, through a mechanism that involves monocyte-derived macrophages.

    • Neta Rosenzweig
    • , Raz Dvir-Szternfeld
    • , Afroditi Tsitsou-Kampeli
    • , Hadas Keren-Shaul
    • , Hila Ben-Yehuda
    • , Pierre Weill-Raynal
    • , Liora Cahalon
    • , Alex Kertser
    • , Kuti Baruch
    • , Ido Amit
    • , Assaf Weiner
    •  & Michal Schwartz
  • Article | | open

    Fibrinogen-like protein 2 (FGL2) mediates immune suppression in glioblastoma (GBM). Here, the authors show that FGL-2 expressed by GBM cancer cells acts by suppressing the differentiation of CD103+ DC cells required to activate the anti-tumor CD8+ T cell response via blocking GM-CSF signalling at NFKB, STAT1/5 and p38 level.

    • Jun Yan
    • , Qingnan Zhao
    • , Konrad Gabrusiewicz
    • , Ling-Yuan Kong
    • , Xueqing Xia
    • , Jian Wang
    • , Martina Ott
    • , Jingda Xu
    • , R. Eric Davis
    • , Longfei Huo
    • , Ganesh Rao
    • , Shao-Cong Sun
    • , Stephanie S. Watowich
    • , Amy B. Heimberger
    •  & Shulin Li
  • Article | | open

    Group 2 innate lymphoid cells (ILC2) are important mediators for allergy, but how ILC2 are regulated under chronic inflammation is still unclear. Here the authors show that Runx transcription factors, which normally suppresses ILC2 activation at steady state, help promote ILC2 activation and type 2 cytokine production in lung allergy mouse models.

    • Chizuko Miyamoto
    • , Satoshi Kojo
    • , Motoi Yamashita
    • , Kazuyo Moro
    • , Georges Lacaud
    • , Katsuyuki Shiroguchi
    • , Ichiro Taniuchi
    •  & Takashi Ebihara
  • Article | | open

    In atherosclerotic plaques, transformation of macrophages into foam cells is a key step in initiating the inflammatory response. Here Fan et al. show that casein kinase 2-interacting protein-1 (CKIP-1) limits foam cell formation and atherosclerosis by preventing expression of the scavenger receptor LOX-1 through REGγ-mediated degradation of Oct-1.

    • Jiao Fan
    • , Lifeng Liu
    • , Qingyan Liu
    • , Yu Cui
    • , Binwei Yao
    • , Minghua Zhang
    • , Yabing Gao
    • , Yesheng Fu
    • , Hongmiao Dai
    • , Jingkun Pan
    • , Ya Qiu
    • , Cui Hua Liu
    • , Fuchu He
    • , Yu Wang
    •  & Lingqiang Zhang
  • Article | | open

    Adoptive cell therapy (ACT) using neoantigen-specific T cells can lead to tumor regression. Here the authors use an in vitro stimulation approach to isolate tumor specific memory T cells from peripheral blood of metastatic epithelial cancer patients targeting unique as well as shared mutations in the KRAS oncogene.

    • Gal Cafri
    • , Rami Yossef
    • , Anna Pasetto
    • , Drew C. Deniger
    • , Yong-Chen Lu
    • , Maria Parkhurst
    • , Jared J. Gartner
    • , Li Jia
    • , Satyajit Ray
    • , Lien T. Ngo
    • , Mohammad Jafferji
    • , Abraham Sachs
    • , Todd Prickett
    • , Paul F. Robbins
    •  & Steven A. Rosenberg
  • Article | | open

    Transcription factors of the AP-1 family can play diverse roles despite recognizing the same DNA sequence. Here the authors investigate the DNA binding activities of AP-1 members in mouse macrophages and apply a machine learning approach to identify motifs predicted to drive factor-specific binding profiles.

    • Gregory J. Fonseca
    • , Jenhan Tao
    • , Emma M. Westin
    • , Sascha H. Duttke
    • , Nathanael J. Spann
    • , Tobias Strid
    • , Zeyang Shen
    • , Joshua D. Stender
    • , Mashito Sakai
    • , Verena M. Link
    • , Christopher Benner
    •  & Christopher K. Glass
  • Article | | open

    The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

    • Luke Whitesell
    • , Nicole Robbins
    • , David S. Huang
    • , Catherine A. McLellan
    • , Tanvi Shekhar-Guturja
    • , Emmanuelle V. LeBlanc
    • , Catherine S. Nation
    • , Raymond Hui
    • , Ashley Hutchinson
    • , Cathy Collins
    • , Sharanya Chatterjee
    • , Richard Trilles
    • , Jinglin L. Xie
    • , Damian J. Krysan
    • , Susan Lindquist
    • , John A. Porco Jr.
    • , Utpal Tatu
    • , Lauren E. Brown
    • , Juan Pizarro
    •  & Leah E. Cowen
  • Article | | open

    The consequences of microglial activation in the aging human brain remain unknown. This study quantified microglial morphology and density in the elderly human brain to show that cortical microglial activation strongly associates with AD pathogenesis and may be an upstream contributor to cognitive decline via the accumulation of tau pathology.

    • Daniel Felsky
    • , Tina Roostaei
    • , Kwangsik Nho
    • , Shannon L. Risacher
    • , Elizabeth M. Bradshaw
    • , Vlad Petyuk
    • , Julie A. Schneider
    • , Andrew Saykin
    • , David A. Bennett
    •  & Philip L. De Jager
  • Article | | open

    Some perinatally HIV infected children who have received early antiretroviral therapy (ART) show long-term sustained virological control after ART cessation. Here the authors describe a case who, at age 9.5 years, shows normal CD4:CD8 T cell ratios and has no detectable levels of replication-competent virus.

    • Avy Violari
    • , Mark F. Cotton
    • , Louise Kuhn
    • , Diana B. Schramm
    • , Maria Paximadis
    • , Shayne Loubser
    • , Sharon Shalekoff
    • , Bianca Da Costa Dias
    • , Kennedy Otwombe
    • , Afaaf Liberty
    • , James McIntyre
    • , Abdel Babiker
    • , Diana Gibb
    •  & Caroline T. Tiemessen
  • Article | | open

    GWAS have led to the identification of 49 genetic loci associated with vitiligo. Here, the authors observe a bimodal distribution of age-of-onset and find a novel genetic locus specifically associated with early-onset vitiligo, located in a regulatory element in the MHC class II region.

    • Ying Jin
    • , Genevieve H. L. Roberts
    • , Tracey M. Ferrara
    • , Songtao Ben
    • , Nanja van Geel
    • , Albert Wolkerstorfer
    • , Khaled Ezzedine
    • , Janet Siebert
    • , Charles P. Neff
    • , Brent E. Palmer
    • , Stephanie A. Santorico
    •  & Richard A. Spritz
  • Article | | open

    The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

    • Bing Liu
    • , Oscar C. Salgado
    • , Sangya Singh
    • , Keli L. Hippen
    • , Jason C. Maynard
    • , Alma L. Burlingame
    • , Lauren E. Ball
    • , Bruce R. Blazar
    • , Michael A. Farrar
    • , Kristin A. Hogquist
    •  & Hai-Bin Ruan
  • Article | | open

    Giardia lamblia express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host´s intestine. Here the authors show that stability and immunomodulatory properties of VSPs can be exploited to both protect and adjuvant vaccine antigens for oral administration.

    • Marianela C. Serradell
    • , Lucía L. Rupil
    • , Román A. Martino
    • , César G. Prucca
    • , Pedro G. Carranza
    • , Alicia Saura
    • , Elmer A. Fernández
    • , Pablo R. Gargantini
    • , Albano H. Tenaglia
    • , Juan P. Petiti
    • , Renata R. Tonelli
    • , Nicolás Reinoso-Vizcaino
    • , José Echenique
    • , Luciana Berod
    • , Eliane Piaggio
    • , Bertrand Bellier
    • , Tim Sparwasser
    • , David Klatzmann
    •  & Hugo D. Luján
  • Article | | open

    Immune recognition of Influenza B virus (IBV) is poorly understood. Here, Liu et al. use flow cytometry to characterize IBV-specific memory B cell responses following seasonal vaccination and show that elicited cross-reactive antibodies can protect against infection, providing a platform for vaccine design.

    • Yi Liu
    • , Hyon-Xhi Tan
    • , Marios Koutsakos
    • , Sinthujan Jegaskanda
    • , Robyn Esterbauer
    • , Danielle Tilmanis
    • , Malet Aban
    • , Katherine Kedzierska
    • , Aeron C. Hurt
    • , Stephen J. Kent
    •  & Adam K. Wheatley