Innate immunity articles within Nature Communications

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  • Article
    | Open Access

    Ubiquitination has an important function in the regulation of antiviral immunity involving the signalling molecule MAVS. Here the authors investigate deubiquitinating enzymes and show USP18 regulates MAVS mediated antiviral signalling through modulating the ubiquitination of MAVS via promotion of interaction between MAVS and TRIM31.

    • Jinxiu Hou
    • , Lulu Han
    •  & Chengjiang Gao

  • Article
    | Open Access

    IFNy can polarize macrophages in the tumour microenvironment to an inflammatory state and thereby contributes to their anti-tumour function. Here the authors show an underlying mechanism in this process is IFNy-driven STAT1 occupancy and activation of NRE1, a regulatory region within the NAMPT gene, thereby implicating inducible NAD salvage synthesis in TAM functions.

    • Thomas B. Huffaker
    • , H. Atakan Ekiz
    •  & Ryan M. O’Connell

  • Article
    | Open Access

    MAL and MyD88 are downstream adaptors of Toll-like receptors (TLR) and the MAL TIR domain forms filaments in vitro, which in turn nucleate the assembly of crystalline arrays of the MyD88 TIR domain. Here, the authors present the structure of these MyD88 TIR crystalline arrays solved by both microcrystal electron diffraction and serial femtosecond crystallography, and they show with mutagenesis experiments that MyD88 interface residues are important for TLR4 signaling in vivo.

    • Max T. B. Clabbers
    • , Susannah Holmes
    •  & Thomas Ve

  • Article
    | Open Access

    Conventional T cell subsets are selected in the thymus by peptide bearing MHC expressed by cortical epithelial cells, in contrast cortical thymocytes express non-peptide bearing MHC molecules including CD1d and MR1 and select iNKT and MAIT cell populations respectively. Here, the authors generate a novel inducible MHC class-I trasnactivator murine system and suggest the absence of peptide-MHC on thymocytes is involved in the selection of non-peptide specific lymphocytes.

    • Hristo Georgiev
    • , Changwei Peng
    •  & Kristin A. Hogquist

  • Article
    | Open Access

    Mycobacterial cell wall lipids can drive immunoevasion, but underlying mechanisms are incompletely understood. Here the authors show TREM2 is a pattern recognition receptor that binds non-glycosylated mycolic acid-containing lipids and inhibits Mincle-induced anti-mycobacterial macrophage responses.

    • Ei’ichi Iizasa
    • , Yasushi Chuma
    •  & Hiromitsu Hara

  • Article
    | Open Access

    PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

    • Stephen Watt
    • , Louella Vasquez
    •  & Nicole Soranzo

  • Article
    | Open Access

    KIR2DL2 and KIR2DL3 are two inhibitory members of the killer-cell immunoglobulin-like receptors (KIR) family that share a common HLA-I preference in binding HLA from the C1 group. However, it is still unclear to what extent binding and function is equivalent between KIR2DL2 and 2DL3. Here, the authors present the crystal structures of KIR2DL2 and 2DL3 in complex with HLA-C*07:02 and observe differences in HLA-C recognition between KIR2DL2 and 2DL3, which correlates with differences in HLA-C binding preference as they show with mutagenesis and binding studies.

    • Shoeib Moradi
    • , Sanda Stankovic
    •  & Julian P. Vivian

  • Article
    | Open Access

    Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3’ untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.

    • Cheryl Q. E. Lee
    • , Baptiste Kerouanton
    •  & Lena Ho

  • Article
    | Open Access

    N6-methyladenosine (m6A) RNA modification regulates RNA metabolism, and has been implicated in immune regulation. Here, the authors show that the m6A methyltransferase, METTL3, translocates into the cytoplasm to increase viral RNA m6A modification, decreases viral ds RNA content, and thereby dampens the RIG/MDA5-induced anti-viral immunity.

    • Weinan Qiu
    • , Qingyang Zhang
    •  & Pengyuan Yang

  • Article
    | Open Access

    NF-κB signalling is critical to TLR mediated cytokine release in various immune responses. Here the authors show how N4BP1 inhibits NEMO signalling and subsequent NF-κB activation and how this pathway is negatively regulated by caspase-8 cleavage of N4BP1.

    • Hexin Shi
    • , Lei Sun
    •  & Bruce Beutler

  • Article
    | Open Access

    Secreted peptides and cell-surface localized receptor kinases allow plants to modify growth and development according to external cues. Here, Rhodes et al. show that the MIK2 receptor perceives the SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) family of phytocytokines and is capable of recognising Fusarium-derived SCOOP-like peptides.

    • Jack Rhodes
    • , Huanjie Yang
    •  & Cyril Zipfel

  • Article
    | Open Access

    Macrophages can be polarized by in vitro culture stimuli into M1 or M2 cells, but microenvironments in vivo are more complex. Here the authors analyze cultured macrophages stimulated with a combination of M1 and M2 stimuli by single-cell RNA sequencing, machine learning, and single-cell secretion profiling to show a surprising level of heterogeneity of response.

    • Andrés R. Muñoz-Rojas
    • , Ilana Kelsey
    •  & Kathryn Miller-Jensen

  • Article
    | Open Access

    Pathogen triggered N-terminal degradation of NLRP1 and CARD8 by the proteasome releases their C-terminal UPA-CARD fragments (CT) to form the inflammasome, which in turn activates caspase-1. Here, the authors present the cryo-EM structures of the NLRP1-CT and CARD8-CT helical filaments as well as the ASC−caspase-1 octamer structure, which together with in vitro and cell based assays provide further insights into the architecture and specificity of the active NLRP1 and CARD8 inflammasomes.

    • L. Robert Hollingsworth
    • , Liron David
    •  & Hao Wu

  • Article
    | Open Access

    COPA regulates Golgi to ER transport, and mutations lead to autoinflammation and disease through poorly understood mechanisms. Here, the authors show that disease-causing COPA variants prevent STING transport from the Golgi to the ER, leading to cGAS-independent activation of the STING pathway.

    • Kojiro Mukai
    • , Emari Ogawa
    •  & Tomohiko Taguchi

  • Article
    | Open Access

    Histones, proteins that bind DNA, are toxic for pathogens outside cells but can also cause multi-organ damage as seen in sepsis. Here the authors develop small negatively charged molecules that can be used as histone antidotes, and show that they improve the phenotype in mouse models with histone-related pathologies.

    • Connor H. O’ Meara
    • , Lucy A. Coupland
    •  & Christopher R. Parish

  • Article
    | Open Access

    lncRNAs are transcriptional regulators, but little is known of them functioning as negative feedback regulators of inflammation in humans. Here, the authors show that the human lncRNA LUCAT1 sequesters STAT1 to limit JAK/STAT signaling and the inflammatory response to viral infection or TLR stimulation in myeloid cells.

    • Shiuli Agarwal
    • , Tim Vierbuchen
    •  & Katherine A. Fitzgerald

  • Article
    | Open Access

    Here, Fahlberg et al. describe the cellular immune response during acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates. The study identifies associations of monocytes and macrophage subtypes in lungs with disease outcome, IL-6 and IL-10 ratio in plasma, and viral replication in bronchial brushes.

    • M. D. Fahlberg
    • , R. V. Blair
    •  & M. Vaccari

  • Article
    | Open Access

    Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.

    • Yihua Zhang
    • , Manman Li
    •  & Dapeng Yan

  • Article
    | Open Access

    The human skin is a highly complex organ comprising multiple tissue layers and diverse cell types. Here, the authors present a spatially-resolved quantitative proteomic atlas of the healthy human skin, characterizing the protein profiles of four skin layers and nine cell types.

    • Beatrice Dyring-Andersen
    • , Marianne Bengtson Løvendorf
    •  & Matthias Mann

  • Article
    | Open Access

    MAVS and MITA are adapter proteins that play distinct roles in the context of the host response to RNA and DNA viruses, respectively. Here the authors implicate RNF115 in dual temporal and spatial mechanisms of interacting and catalyzing distinct ubiquitination of MAVS and MITA to modulate RNA and DNA antiviral immune responses.

    • Zhi-Dong Zhang
    • , Tian-Chen Xiong
    •  & Bo Zhong

  • Article
    | Open Access

    How mutations in the microbial receptor NOD2 induce Blau syndrome in humans and related uveitis is unclear. Here the authors show, using Nod2-deficient mice and experimental uveitis, that Nod2 negatively regulates T cell activation and transcription of autoimmunity-related genes to suppress Th17 responses and uveitis.

    • Ruth J. Napier
    • , Ellen J. Lee
    •  & Holly L. Rosenzweig

  • Article
    | Open Access

    A series of Toll-like receptor 7 (TLR7)-specific antagonists and extensive structural analysis reveal the open conformation of the receptor and the structural basis of TLR7 antagonism. One of the compounds shows efficacy in treating mouse model of systemic lupus erythematosus.

    • Shingo Tojo
    • , Zhikuan Zhang
    •  & Toshiyuki Shimizu

  • Article
    | Open Access

    Macrophages survey their surroundings using macropinocytosis, but its regulation is unclear. Here, the authors report that SLIT2, a known inhibitor of Rac GTPases, is an endogenous inhibitor of macropinocytosis, and that SLIT2 limits the uptake of NOD2 ligands into immune cells and subsequent release of the inflammatory chemokine, CXCL1, in vivo.

    • Vikrant K. Bhosle
    • , Tapas Mukherjee
    •  & Lisa A. Robinson

  • Article
    | Open Access

    The pandemic of SARS-CoV-2 post a significant threat to public health. Here the authors show, by screening 23 viral proteins, that both structural and non-structural SARS-CoV-2 proteins are capable of modulating host innate immunity and type interferon responses, with this information serves to warrant further studies on SARS-CoV-2 pathogenesis.

    • Xiaobo Lei
    • , Xiaojing Dong
    •  & Jianwei Wang

  • Article
    | Open Access

    TLR4 signalling can reprogram the metabolism of macrophages to be more glycolytic and proinflammatory. Here the authors show that LPS and TLR4 signalling results in recruitment of TBK1, which in turn phosphorylates serine 727 on STAT3 to enable a proinflammatory switch via an effect on mitochondrial metabolism.

    • Jesse J. Balic
    • , Hassan Albargy
    •  & Ashley Mansell

  • Article
    | Open Access

    Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.

    • Gael Boivin
    • , Julien Faget
    •  & Etienne Meylan

  • 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
    •  & Christine Skerka

  • 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
    •  & Trude H. Flo

  • 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
    •  & Xuebin Qin

  • 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
    •  & Jenny P. -Y. Ting

  • 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
    •  & Philip Goulder

  • Article
    | Open Access

    Oncogenic Ras mutations are common drivers in myeloid leukemia. Here, the authors show in patient cells and in mice that oncogenic K-Ras activates NLRP3 inflammasome to drive myeloproliferation, which can be reversed by genetic or pharmacologic NLRP3 blockade.

    • Shaima’a Hamarsheh
    • , Lena Osswald
    •  & Robert Zeiser

  • Article
    | Open Access

    The Bacillus haemolytic enterotoxin haemolysin BL has been shown to activate the NLRP3 inflammasome. Here the authors show that a non-haemolytic enterotoxin (NHE) from B. cereus can also activate the NLRP3 inflammasome with a similar mechanism of lytic pore formation.

    • Daniel Fox
    • , Anukriti Mathur
    •  & Si Ming Man

  • Article
    | Open Access

    Here, using longitudinal pre- and post-infection samples from the RV217 Early Capture HIV Cohort Study, the authors show that mucosa-associated invariant T (MAIT) cells become activated and expand during the early acute phase of HIV infection, with subsequent reprogramming towards innate-like functionality.

    • Kerri G. Lal
    • , Dohoon Kim
    •  & Johan K. Sandberg

  • Article
    | Open Access

    Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

    • Franziska Herster
    • , Zsofia Bittner
    •  & Alexander N. R. Weber

  • Article
    | Open Access

    Toll-like receptor TLR5 recognizes a domain, D1, that is present in flagellins of several pathogenic bacteria but not in Helicobacter pylori. Here, the authors show that TLR5 can be activated independently of flagellin by a component of the H. pylori type IV secretion system that contains a D1-like motif.

    • Suneesh Kumar Pachathundikandi
    • , Nicole Tegtmeyer
    •  & Steffen Backert

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