Innate immune cells articles within Nature Communications

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  • Article
    | Open Access

    Epithelial tissue mononuclear phagocytes (MNP) can transmit HIV to CD4 T cells, but less is known about sub-epithelial cells. Here, the authors describe MNPs in human anogenital and colorectal tissues and find that CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 preferentially take up and transmit HIV.

    • Jake W. Rhodes
    • , Rachel A. Botting
    •  & Andrew N. Harman

  • Article
    | Open Access

    Here, the authors combine 16 S rRNA sequencing, culture and bioinformatics to profile the microbiome in 234 serial bronchoalveolar lavage samples from 64 lung transplant recipients collected over 49-months and identify distinct compositional states, termed pneumotypes, linked to current health status, and establish a collection of primary lung bacterial isolates, LuMiCol.

    • Sudip Das
    • , Eric Bernasconi
    •  & Laurent P. Nicod

  • Article
    | Open Access

    Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.

    • Anne Kathrin Lösslein
    • , Florens Lohrmann
    •  & Philipp Henneke

  • Article
    | Open Access

    Cardiac immune cells play various roles in the maintenance of homeostasis and diseases in the heart. Here the authors show that cardiac resident macrophages are a critical regulator of cardiac impulse conduction through amphiregulin production, contributing to the prevention of sudden death.

    • Junichi Sugita
    • , Katsuhito Fujiu
    •  & Issei Komuro

  • Article
    | Open Access

    Innate lymphoid cells (ILCs) are important regulators of biological processes. Here the authors combine multiplexed imaging and computational pipelines to reveal tonsillar IRF4+ ILC3s, and to identify conserved stromal landmarks for ILC localization, thereby providing a platform for future ILC studies.

    • Anna Pascual-Reguant
    • , Ralf Köhler
    •  & Anja E. Hauser

  • Article
    | Open Access

    The peritoneal cavity is a complicated myeloid niche containing a mixed population of resident macrophages and infiltrating cells that are responsive to inflammatory cues. Here the authors trace the fate of these infiltrating macrophages, their conversion to resident cells and how this is altered by the local inflammatory state over time.

    • P. A. Louwe
    • , L. Badiola Gomez
    •  & S. J. Jenkins

  • 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

    Neutrophils secrete numerous immune effector molecules including cathelicidin which is associated with antimicrobial properties. Here the authors implicate neutrophil derived cathelicidin in modulation of CD4 T cell homoeostasis and the promotion of Th17 CD4 T cells.

    • Danielle Minns
    • , Katie J. Smith
    •  & Emily Gwyer Findlay

  • Article
    | Open Access

    Myeloid cells are able to utilize a variety of monosaccharides from our diet, including fructose. Here the authors show that when monocytes are reliant on fructose as a carbon energy source they are reprogrammed towards oxidative metabolism, glutamine anaplerosis and a pro-inflammatory phenotype owing to excess pro-inflammatory cytokine production.

    • Nicholas Jones
    • , Julianna Blagih
    •  & Catherine A. Thornton

  • Article
    | Open Access

    Bulk and single-cell transcriptomic data can be a source of novel insights into how cells interact with each other. Here the authors develop ICELLNET, a global, biologically validated, and easy-to-use framework to dissect cell communication from individual or multiple cell-based transcriptomic profiles.

    • Floriane Noël
    • , Lucile Massenet-Regad
    •  & Vassili Soumelis

  • Article
    | Open Access

    Macrophages may polarize into different states with distinct regulatory functions for inflammation. Here the authors perform high-throughput in vitro screening of a library of ~4000 compounds to identify those with specific effects on human macrophage polarization, while RNAseq helps uncover the targets and pathways mediating these effects.

    • Guangan Hu
    • , Yang Su
    •  & Jianzhu Chen

  • Article
    | Open Access

    The tumor microenvironment is composed of many cell types that crosstalk to modulate local immunity. Here the authors show that Amyloid β proteins from cancer-associated fibroblasts (CAF) induce neutrophil extracellular trap (NET) production by neutrophils, while NET feeds back to activate CAF, thereby implicating Amyloid β as a potential therapy target.

    • Hafsa Munir
    • , James O. Jones
    •  & Jacqueline D. Shields

  • Article
    | Open Access

    Type 2 conventional dendritic cells (cDC2) are important immune activators in adults, but their development and functions at the neonatal stage remain unclear. Here the authors show, using fate-mapping and single-cell RNA sequencing, that neonatal cDC2 come from multiple origins, but converge functionally as potent immune activators upon proper stimuli.

    • Nikos E. Papaioannou
    • , Natallia Salei
    •  & Barbara U. Schraml

  • Article
    | Open Access

    RAGE signalling is implicated in sepsis. Here the authors use T7 phage display to identify SLP76 as a binding partner for the cytosolic tail of RAGE and provide a reagent that can block this interaction and protect mice from sepsis in a caecal ligation and puncture model.

    • Zhengzheng Yan
    • , Haihua Luo
    •  & Yong Jiang

  • Article
    | Open Access

    Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

    • Rajasekharan Somasundaram
    • , Thomas Connelly
    •  & Meenhard Herlyn

  • 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

    TARM1 is a LILR family member that drives cell signalling via interactions with FcRγ. Here the authors show that TARM1 binds collagens to activate dendritic cells and thereby is an effector of inflammatory arthritis, plus provide a soluble TARM-Fc fusion protein that can limit collagen-induced arthritis in mice.

    • Rikio Yabe
    • , Soo-Hyun Chung
    •  & Yoichiro Iwakura

  • Article
    | Open Access

    Blood eosinophil (EOS) counts may serve as risk factors for human coronary heart diseases. Here the authors show that increased circulating and myocardial EOS after myocardial infarction play a cardioprotective role by reducing cardiomyocyte death, cardiac fibroblast activation and fibrosis, and endothelium activation-mediated inflammatory cell accumulation.

    • Jing Liu
    • , Chongzhe Yang
    •  & Guo-Ping Shi

  • Article
    | Open Access

    Mannose is present at trace levels in blood and regulates cancer growth. Here the authors show that supraphysiological levels of mannose can also regulate macrophages, limiting their production of IL-1β and increasing resistance of mice to LPS-induced endotoxemia and DSS-induced colitis.

    • Simone Torretta
    • , Alessandra Scagliola
    •  & Simone Cardaci

  • Article
    | Open Access

    Inhibition of the metabolic enzyme ATP-citrate lyase can attenuate atherosclerosis by preventing dyslipidemia and potentially also by reducing macrophage-mediated inflammation. Here, the authors show that specific targeting of ACLY in macrophages results in more stable atherosclerotic plaques.

    • Jeroen Baardman
    • , Sanne G. S. Verberk
    •  & Jan Van den Bossche

  • Article
    | Open Access

    CD40L-expressing chimeric antigen receptor (CAR) T cells show enhanced anti-tumor immunity, but the cellular mechanisms are still unclear. Here we show, by analyzing mice deficient of conventional dendritic cell type 1 (cDC1) that cDC1s are induced by CD40L+ CAR T cells to prime endogenous CD8 T cells for a stronger anti-tumor immune response.

    • Nicholas F. Kuhn
    • , Andrea V. Lopez
    •  & Renier J. Brentjens

  • Article
    | Open Access

    Type I interferon drives autoimmune pathology in SLE and has been assumed to come predominantly from plasmacytoid dendritic cells (pDCs). Here, the authors show that prior to the onset of SLE, pDCs lose multiple immunogenic functions and, instead, non-hematopoietic cells such as keratinocytes are a major source of type I interferons.

    • Antonios Psarras
    • , Adewonuola Alase
    •  & Edward M. Vital

  • Article
    | Open Access

    Tumour-infiltrating lymphocytes play a crucial role in neuroblastoma, but their relationship to other immune cells is poorly understood. Here the authors identify the cellular and gene signatures of intratumoural dendritic cells and natural killer cells that predict the clinical outcome of neuroblastoma.

    • Ombretta Melaiu
    • , Marco Chierici
    •  & Doriana Fruci

  • Article
    | Open Access

    Inflammation contributes to the development of metabolic disease through incompletely understood mechanisms. Here the authors report that deletion of the transcription factor KLF2 in myeloid cells leads to increased feeding and weight gain in mice with concomitant peripheral and central tissue inflammation, while overexpression protects against diet-induced metabolic disease.

    • David R. Sweet
    • , Neelakantan T. Vasudevan
    •  & Mukesh K. Jain

  • Article
    | Open Access

    Systemic sclerosis (SSc) is a disease with manifestation in the skin and immune etiology, but the pathogenic immune cell types remain unidentified. Here the authors use ATAC-seq to profile chromatin landscapes of skin samples from patients with SSc to implicate skin dendritic cells for having the strongest disease-associated epigenetic changes.

    • Qian Liu
    • , Lisa C. Zaba
    •  & Howard Y. Chang

  • Article
    | Open Access

    Necrotizing Enterocolitis (NEC) is an untreatable intestinal disease in infants. Here the authors show that human and experimental mouse NEC is associated with altered toll-like receptor expression in the intestine, enhanced Th17/type 3 polarization in adaptive immune and innate lymphoid cells, dysregulated microbiota, and reduced interleukin-37 signaling.

    • Steven X. Cho
    • , Ina Rudloff
    •  & Marcel F. Nold

  • Article
    | Open Access

    Antigen presenting cells induce CD4+ T helper (Th) differentiation upon pathogen encounters. Here the authors use fluorescently-labeled bacteria, helminth and fungi to track and describe the functions of IRF4+ migratory type 2 dendritic cells and monocytes in the specific induction of Th1, Th2 or Th17 responses following skin inoculation.

    • Kerry L. Hilligan
    • , Shiau-Choot Tang
    •  & Franca Ronchese

  • Article
    | Open Access

    Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration.

    • Rania Dagher
    • , Alan M. Copenhaver
    •  & Marina Pretolani

  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.

    • Pedram Shafiei-Jahani
    • , Benjamin P. Hurrell
    •  & Omid Akbari

  • Article
    | Open Access

    Arterial macrophages develop from either yolk sac or bone marrow progenitors. Here, the author show that ageing-induced reduction of arterial macrophages is not replenished by bone marrow-derived cells, but under inflammatory conditions circulating monocytes are recruited to maintain homeostasis, while arterial macrophages of yolk sac origin carry out tissue repair.

    • Tobias Weinberger
    • , Dena Esfandyari
    •  & Christian Schulz

  • Article
    | Open Access

    Anti-androgen therapy inhibits prostate cancer (PC) progression, and is thought to act directly on cancer cells. Here the authors show that androgen receptor is expressed on normal and PC-associated macrophages, and its stimulation alters macrophage secretome to promote migration of cultured PC cell lines.

    • Bianca Cioni
    • , Anniek Zaalberg
    •  & Andries M. Bergman

  • Article
    | Open Access

    How the Drosophila lymph gland hemocytes develop and are regulated at a single-cell level is unclear. Here, the authors use single-cell RNA sequencing to show heterogeneity of developing hemocytes in the lymph gland and how they react to wasp infestation, and compare hemocytes from two independent origins.

    • Bumsik Cho
    • , Sang-Ho Yoon
    •  & Jiwon Shim

  • Article
    | Open Access

    The developmental origins and functions of testis macrophages remain incompletely characterized. Here, the authors show, using histology, high-dimensional mass cytometry and cell fate-mapping data, that interstitial and peritubular macrophages originate from distinct precursors and contribute distinctly to spermatogenesis.

    • Emmi Lokka
    • , Laura Lintukorpi
    •  & Marko Salmi

  • Article
    | Open Access

    Innate T cells such as iNKT, MAIT and γδ T cells all develop in the thymus, but their differentiation paths are still unclear. Here, the authors show, using single-cell RNA sequencing, that all three cell types develop via shared and branched differentiation paths that are corroborated by additional results from gene-deficient mice and human liver T cells.

    • Minji Lee
    • , Eunmin Lee
    •  & You Jeong Lee

  • Article
    | Open Access

    Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

    • Jasper Iske
    • , Midas Seyda
    •  & Stefan G. Tullius

  • 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

    Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA, circKcnt2, to be induced in ILC3s from inflamed gut, yet circKcnt2 deletion aggravates mouse experimental colitis, thereby implicating circKcnt2 as a potential feedback regulator of ILC3 activation and gut immunity.

    • Benyu Liu
    • , Buqing Ye
    •  & Zusen Fan

  • Article
    | Open Access

    As macrophages switch to a proinflammatory gylcolytic state they start to generate triglyceride-rich lipid droplets, but what function these droplets have in this context is not clear. Here the authors show that this triglyceride synthesis is requisite for prostaglandin E2 production and subsequent inflammatory activation.

    • Angela Castoldi
    • , Lauar B. Monteiro
    •  & Edward J. Pearce

  • Article
    | Open Access

    PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice and provide evidence that PD-1 signaling alters ILC2 function by modulation of cell metabolism.

    • Doumet Georges Helou
    • , Pedram Shafiei-Jahani
    •  & Omid Akbari

  • Article
    | Open Access

    Tocilizumab has been used to treat the excessive inflammatory responses in COVID-19 patients. Here, the authors use single-cell RNA sequencing results from two severe COIVD-19 patients to provide high-dimensional immune profiling data, and to implicate potential cellular and molecular insights for the therapeutic effects of tocilizumab.

    • Chuang Guo
    • , Bin Li
    •  & Kun Qu

  • Article
    | Open Access

    Inflammation, immune cells and the host microbiota are intimately linked in the pathophysiology of obesity and diabetes. Here the authors show mucosal-associated invariant T cells fuel inflammation in the tissues and serve a function in promoting metabolic breakdown, polarising macrophage populations and inducing dysbiosis of the intestinal microbiota.

    • Amine Toubal
    • , Badr Kiaf
    •  & Agnès Lehuen

  • Article
    | Open Access

    Kupffer cells are more resistant to M. tuberculosis when compared with alveolar macrophages. Here the authors show that this distinction is caused by the presence of ornithine and imidazole in Kupffer cells and that these metabolites can drive autophagy and M. tuberculosis killing in alveolar macrophages when given intranasally to infected mice.

    • Ramya Sivangala Thandi
    • , Rajesh Kumar Radhakrishnan
    •  & Ramakrishna Vankayalapati

  • Article
    | Open Access

    Lactate is a by-product of glycolysis that can function via its G protein receptor GPR81. Here the authors show that LPS or Salmonella infection enhances glycolytic metabolism in bone marrow neutrophils, resulting in lactate production, which increases endothelial barrier permeability and mobilization of these neutrophils by targeting endothelial GPR81.

    • Eman Khatib-Massalha
    • , Suditi Bhattacharya
    •  & Tsvee Lapidot

  • Article
    | Open Access

    Altered monocyte responses and testosterone levels correlate, individually, with the pathogenesis of hepatic amebiasis in mice. Here the authors show that testosterone induces enhanced TNF/CXCL1 expression and stronger proinflammatory responses in both human and mouse monocytes to support an androgen-monocyte axis of inflammation regulation.

    • Julie Sellau
    • , Marie Groneberg
    •  & Hannelore Lotter

  • Article
    | Open Access

    CD4+ T cells contain a T-bethigh memory-phenotype (MP) population with innate-like functions. Here the authors characterize the requirements for their differentiation at homeostasis and identify a function for IL-12 that is tonically produced by type 1 dendritic cells in an MyD88- and CD40-dependent, but foreign PAMP-independent manner.

    • Takeshi Kawabe
    • , Jaeu Yi
    •  & Alan Sher

  • Article
    | Open Access

    Chemical tools to monitor drug-target engagement of endogenous enzymes are essential for preclinical target validation. Here, the authors present a chemical genetics strategy to study target engagement of endogenous kinases, achieving specific labeling and inactivation of FES kinase to provide insights into FES’ role in neutrophil phagocytosis.

    • Tom van der Wel
    • , Riet Hilhorst
    •  & Mario van der Stelt

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