Immunology articles within Nature Communications

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  • Article
    | Open Access

    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
    •  & Jianke Zhang
  • Article
    | Open Access

    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
    •  & Joachim R. de Miranda
  • Article
    | Open Access

    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
    •  & Ashley L. St. John
  • Article
    | Open Access

    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
    •  & Yatrik M. Shah
  • Article
    | Open Access

    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
    •  & Patrick J. Brennan
  • Article
    | Open Access

    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
    •  & Jan Rybniker
  • Article
    | Open Access

    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
    •  & S. Munir Alam
  • Article
    | Open Access

    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
    •  & Gur Yaari
  • Article
    | Open Access

    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
    •  & Valbona Mirakaj
  • Article
    | Open Access

    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
    •  & Philip M. Murphy
  • Article
    | Open Access

    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
    •  & Derrick J. Rossi
  • Article
    | Open Access

    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
    •  & Michael Shapira
  • Article
    | Open Access

    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
    •  & James G. Beeson
  • Article
    | Open Access

    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
    •  & David Masopust
  • Article
    | Open Access

    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
    •  & Keiji Hirota
  • Article
    | Open Access

    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
    •  & Karl-Johan Malmberg
  • Article
    | Open Access

    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
    •  & Andrew P. Cope
  • Article
    | Open Access

    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
    •  & Takashi Ebihara
  • Article
    | Open Access

    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
    •  & Lingqiang Zhang
  • Article
    | Open Access

    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
    •  & Steven A. Rosenberg
  • Article
    | Open Access

    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
    •  & Christopher K. Glass
  • Article
    | Open Access

    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
    •  & Philip L. De Jager
  • Article
    | Open Access

    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
    •  & Caroline T. Tiemessen
  • Article
    | Open Access

    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
    •  & Hai-Bin Ruan
  • Article
    | Open Access

    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
    •  & Hugo D. Luján
  • Article
    | Open Access

    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
    •  & Adam K. Wheatley
  • Article
    | Open Access

    Host metabolic reprogramming plays a role in functional responses against pathogens. Here, the authors characterise malonylated proteins in macrophages and show that malonylation of the glycolytic enzyme GAPDH impacts cytokine production by modulating both its enzymatic activity and RNA-binding capacity.

    • Silvia Galván-Peña
    • , Richard G. Carroll
    •  & Luke A. O’Neill
  • Article
    | Open Access

    Engagement of T cell receptors (TCRs) induces the formation of microclusters that mediate the downstream signalling events. Here the authors show, using high resolution TIRF-SIM and live cell imaging, that ZAP70 and LAT are recruited to TCR with distinct kinetics, with the delayed ZAP70-TCR association modulated by TCR-induced calcium flux.

    • Jason Yi
    • , Lakshmi Balagopalan
    •  & Lawrence E. Samelson
  • Article
    | Open Access

    Zika virus infections can cause devastating congenital birth defects but the underlying interactions with the host immune system are not well understood. Here, the authors examine the immune basis of vaginal protection and susceptibility to Zika viral infection, and identify a hormonal dependent role for interferon-lambda-mediated protection against disease.

    • Elizabeth A. Caine
    • , Suzanne M. Scheaffer
    •  & Michael S. Diamond
  • Article
    | Open Access

    Tissue-resident macrophages are highly specialized phagocytes that serve multiple functions. Here, using high-dimension analyses and fate-mapping experiments, the authors show that fetal liver-derived macrophages dominate the mammary gland in neonatal and adult, and display characteristic phenotypes and functions.

    • Norma Jäppinen
    • , Inês Félix
    •  & Marko Salmi
  • Article
    | Open Access

    Lymphangiogenesis occurs in the context of systemic inflammation and development but has not been reported for the lymphatics that surround the CNS. Here the authors show that in the context of experimental autoimmune encephatlitis, lymphangiogenesis occurs at the cribriform plate, but not the meninges, and contributes to immune cell and antigen drainage.

    • Martin Hsu
    • , Aditya Rayasam
    •  & Zsuzsanna Fabry
  • Article
    | Open Access

    Chronic hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) and is associated with immune tolerance to HBV. Here the authors show, in a transgenic mouse model, that rescuing T cells function via inhibition of co-inhibitory receptor TIGIT results in HCC development via supporting inflammation.

    • Lu Zong
    • , Hui Peng
    •  & Zhigang Tian
  • Article
    | Open Access

    B cells produce antibodies to mediate various immune functions, but are also reported to negatively regulate immune responses. Here, the authors show that a subset of mature B cells expressing low levels of IgD, present in both mice and human, may pursue this regulatory function indirectly by inducing the proliferation of regulatory T cells via GITRL.

    • Avijit Ray
    • , Mohamed I. Khalil
    •  & Bonnie N. Dittel
  • Article
    | Open Access

    Long noncoding RNA (lncRNA) genes do not encode protein products yet are emerging as key regulators of cellular processes such as transcription and translation. Here, by examining lncRNA profiles from human and mouse CD8 T cells, the authors show that stages of CD8+ T cell differentiation are defined by expression of lncRNA genes.

    • William H. Hudson
    • , Nataliya Prokhnevska
    •  & Haydn T. Kissick
  • Article
    | Open Access

    Current experimental monoclonal antibodies (mAbs) for Ebola virus (EBOV) post-exposure immunotherapy are ineffective against Sudan (SUDV) or Marburg virus (MARV). Here, authors develop cocktails of mAbs that protect nonhuman primates against EBOV, SUDV, and MARV infection when given four days post infection.

    • Jennifer M. Brannan
    • , Shihua He
    •  & M. Javad Aman
  • Article
    | Open Access

    Urolithins are microbial metabolites derived from food polyphenols. Here, Singh et al. show that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases.

    • Rajbir Singh
    • , Sandeep Chandrashekharappa
    •  & Venkatakrishna R. Jala
  • Article
    | Open Access

    The Membrane-Proximal External Region (MPER) of the HIV Env gp41 subunit is a target for broadly neutralizing antibodies. Here, the authors apply super-resolution stimulated emission depletion (STED) microscopy on single virions and provide insights into how the MPER epitope is recognized.

    • Pablo Carravilla
    • , Jakub Chojnacki
    •  & José L. Nieva
  • Article
    | Open Access

    The potential links between infections and neurodegenerative disorders are unclear. Here, Wu et al. present a mouse model of low-grade candidemia characterized by highly localized cerebritis, accumulation of amyloid precursor protein and beta peptides, and mild memory impairment that resolves with fungal clearance.

    • Yifan Wu
    • , Shuqi Du
    •  & David B. Corry
  • Article
    | Open Access

    Protective antibody responses depend critically on proper B cell development and differentiation at multiple stages. Here the authors show that a protein arginine methyltransferase, Prmt5 uses multiples pathways to prevent death of immature B cells, yet modulates, in p53-independent manners, the survival and differentiation of mature B cells.

    • Ludivine C. Litzler
    • , Astrid Zahn
    •  & Javier M. Di Noia
  • Article
    | Open Access

    The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.

    • Koen Venken
    • , Peggy Jacques
    •  & Dirk Elewaut
  • Article
    | Open Access

    Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

    • Leonie Brockmann
    • , Shiwa Soukou
    •  & Samuel Huber
  • Article
    | Open Access

    Mutations within immunological epitope containing regions of influenza A virus can impair the established immune response between influenza strains and could impact rational vaccine design. Here Grant et al. examine the presence, structural impact and cross reactivity of two human immunodominant influenza epitope variants.

    • Emma J. Grant
    • , Tracy M. Josephs
    •  & Katherine Kedzierska
  • Article
    | Open Access

    Ezh2 is an histone methyltransferase that catalyzes H3K27me3. Here the authors show that Ezh2 promotes T follicular helper (TFH) differentiation and helper activity, by cooperating with Tcf1 to activate Bcl6 transcription and epigenetically repressing p19Arf, an antagonist of Bcl6 function and TFH cell survival.

    • Fengyin Li
    • , Zhouhao Zeng
    •  & Hai-Hui Xue
  • Article
    | Open Access

    Secreted cytokine decoy receptors encoded by viruses can act as potent immune evasion proteins modulating antiviral immunity. Here Hernaez et al. show that cell surface binding is required for efficient evasion of the host response by a secreted virus encoded type I IFN decoy receptor of vaccinia and ectromelia virus using an in vivo model of infection.

    • Bruno Hernáez
    • , Juan Manuel Alonso-Lobo
    •  & Antonio Alcamí
  • Article
    | Open Access

    The potential impact of neonicotinoid field exposure on bumblebee microbiota remains unclear. In a landscape—scale study, Wintermantel et al. show that whilst exposure to clothianidin impacts Bombus terrestris performance, it does not affect levels of gut bacteria, viruses or intracellular parasites.

    • Dimitry Wintermantel
    • , Barbara Locke
    •  & Joachim R. de Miranda