Mucosal immunology articles within Nature Communications

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  • Article
    | Open Access

    A diverse array of antigens can trigger allergic reactions. Here the authors present the ‘AllerScan’ programmable phage display library, which is an efficient and unbiased approach for profiling anti-allergen antibody reactivities at cohort scale, with which a key wheat epitope is found to distinguish between wheat allergy and tolerance.

    • Daniel R. Monaco
    • , Brandon M. Sie
    •  & H. Benjamin Larman

  • Article
    | Open Access

    Trafficking of IgA/commensal complex in the gut has been implicated in inflammatory bowel diseases such as Crohn’s disease, but molecular insights are still lacking. Here the authors show, using mouse model or human cells, that NOD2 mutation increases IgA transport, potentially by altering gut microfold cells from the gut, to impact gut inflammation.

    • Nicolas Rochereau
    • , Xavier Roblin
    •  & Stéphane Paul

  • Article
    | Open Access

    CD39 is an ectonucleotidase associated with immunoregulatory function. Here authors show regulation of CD39 expression by an endogenous antisense RNA moiety transcribed from the 3‘ end of CD39/ENTPD1 which when itself is silenced results in amelioration of pathology in an animal model of colitis.

    • Rasika P. Harshe
    • , Anyan Xie
    •  & Maria Serena Longhi

  • Article
    | Open Access

    Tissue resident CD8 + T cells present at mucosal surfaces are poised to elicit function in situ, however approaches to boost their number in the gastrointestinal mucosa has been limited. Here the authors combine the use of Listeria monocytogenese and transient depletion of the intestinal microbiome to boost the resident CD8 + T cell response.

    • Simone Becattini
    • , Eric R. Littmann
    •  & Eric G. Pamer

  • Article
    | Open Access

    Butyrophilin-like genes are emerging as central to tissue associated γδ T cell compartments. Here, the authors show that the butyropilin-like gene-products exert their effects as combinatorially diverse heteromers that differentially affect the selection and maintenance of skin-resident and gut-resident intraepithelial γδ T-cell populations.

    • Anett Jandke
    • , Daisy Melandri
    •  & Adrian Hayday

  • 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

    Early postnatal colonization has been described to be critical for the long-term microbiota composition and health. Here, via multi-omics approach, the authors investigate the impact of the developing host hepatic metabolism on the murine intestinal microbiota composition with comparative analysis at immediate postnatal period, early infancy and weaning and adulthood.

    • N. van Best
    • , U. Rolle-Kampczyk
    •  & M. W. Hornef

  • Article
    | Open Access

    Milk breastfeeding and prebiotic-supplemented formulas have varying effects on the infant gut microbiome. Here, in a randomized controlled clinical trial, the authors investigate the effects of a Lactobacillus paracasei-fermented formula on the immune defense mechanisms, microbiota and its metabolome in full term infants.

    • Paola Roggero
    • , Nadia Liotto
    •  & Maria Rescigno

  • 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
    •  & Jenny Mjösberg

  • 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
    •  & Siegfried Hapfelmeier

  • 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
    •  & Alberto Martin

  • 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
    •  & Daniela Finke

  • Article
    | Open Access

    Heterogeneous helper T (Th) cell responses contribute to differential susceptibility to immunological disorders. Here the authors perform haplotype-based computational screens of 16 inbred mouse strains to identify a transcription factor, p73, as an important negative regulator of Th1 differentiation, with p73 deficient mice manifesting alterations in two inflammatory disease models.

    • Min Ren
    • , Majid Kazemian
    •  & Warren J. Leonard

  • Article
    | Open Access

    Lamina propria macrophages are at the frontline of defense against intestinal pathogens. Here the authors reveal that CCR2 and NR4A1-dependent CX3CR1+ macrophages form a dense network around the vessels in the lamina propria, and implicate this anatomical structure into prevention of systemic bacterial dissemination.

    • Masaki Honda
    • , Bas G. J. Surewaard
    •  & Paul Kubes

  • Article
    | Open Access

    Innate lymphoid cells (ILC) are important immune cells for maintaining the gut homeostasis. Here the authors show that c-FLIP, an anti-apoptotic molecule, is important for the development of NKP46+ ILC1, including conventional natural killer (cNK) cells, and ILC3, with cNK being more critical for ameliorating intestinal inflammation.

    • Ute Bank
    • , Katrin Deiser
    •  & Thomas Schüler

  • Article
    | Open Access

    Here Kumar et al. show that increased intestinal permeability reduces hepatic de novo lipogenesis, affecting plasma membrane fluidity and lifespan of RBCs, and the resulting increase in iron levels promotes bacterial growth. This mechanism may explain the increased risk of sepsis associated with inflammatory bowel disease.

    • Manish Kumar
    • , Aralia Leon Coria
    •  & Kris Chadee

  • Article
    | Open Access

    Microfold cells (M cells) sit at the gut epithelial surface to sample antigens and maintain local immune homeostasis. Here the authors show that M cells are feedback-regulated by M cell-originated osteoprotegerin (OPG) to suppress RNAKL-induced M cell differentiation, and that OPG deficiency alters both gut colitis and infection phenotypes.

    • Shunsuke Kimura
    • , Yutaka Nakamura
    •  & Koji Hase

  • Article
    | Open Access

    Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

    • Lenine J. P. Liebenberg
    • , Lyle R. McKinnon
    •  & Quarraisha Abdool Karim

  • Article
    | Open Access

    The role of the transmembrane glycoprotein CD47 in healing injured intestinal mucosa is unclear. Here, the authors show that selective loss of CD47 in the murine intestinal epithelium results in defective mucosal repair after colonic wounding, with suggested impaired cell migration in vitro.

    • Michelle Reed
    • , Anny-Claude Luissint
    •  & Charles A. Parkos

  • Article
    | Open Access

    IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

    • Eirini Giannoudaki
    • , Yasmina E. Hernandez-Santana
    •  & Patrick T. Walsh

  • Article
    | Open Access

    Detailed characterizations of human lung tissue-resident natural killer (trNK) cells, which potentially regulate local immune responses, is still lacking. Here the authors show that lung CD69+ CD16– NK cells express tissue-residency markers, produce effector cytokines, and are distinct, feature-wise, from lung CD8+ memory T cells or trNK in other tissues.

    • Nicole Marquardt
    • , Eliisa Kekäläinen
    •  & Jakob Michaëlsson

  • Article
    | Open Access

    High frequency semen exposure has been associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, Abdulhaqq et al. show that repeated vaginal exposure to semen reduces vaginal infection by SIV in non-human primates, and is associated with lower CCR5 expression in CD4 T-cells and a local type-I interferon response.

    • Shaheed A. Abdulhaqq
    • , Melween Martinez
    •  & Luis J. Montaner

  • Article
    | Open Access

    The effect of diet-induced obesity on intestinal B cell populations is not well understood despite emerging evidence of a critical role for the intestinal immune system in contributing to insulin resistance. Here, the authors show important functions of IgA in regulating metabolic disease and for intestinal immunity in modulating systemic glucose metabolism.

    • Helen Luck
    • , Saad Khan
    •  & Daniel A. Winer

  • Article
    | Open Access

    Group 3 innate lymphoid cells (ILC3s) have important functions in inflammatory bowel disease. Here, the authors show that TL1A/DR3 signalling stimulates ILC3s to produce GM-CSF, thereby recruiting inflammatory cells, which results in subsequent IL-23-dependent loss of ILC3s and further intestinal inflammation.

    • Jingyu Li
    • , Wenli Shi
    •  & Ju Qiu

  • Article
    | Open Access

    Bone marrow-derived monocytes are recruited to the gut to replenish the local macrophage pool. Here the authors show that, while such replenishment constitutively occur under homeostasis, gut inflammation induces an immediate, Trem1-related transcription change to recruited monocyte to enable a context-dependent modulation of macrophage functions.

    • Girmay Desalegn
    •  & Oliver Pabst

  • Article
    | Open Access

    Wormley and colleagues present data showing that vaccine strategies can be devised to prime dendritic cells to respond in a memory-like fashion upon subsequent exposure to a pathogen.

    • Camaron R. Hole
    • , Chrissy M. Leopold Wager
    •  & Floyd L. Wormley Jr.

  • Article
    | Open Access

    Composition and function of immune populations at barrier surfaces is crucial for response to infection. Here, the authors identify a population of dendritic cells in human epidermis, abundant in anogenital epithelia and distinct from Langerhans cells by surface phenotype and by high capacity for HIV infection and transmission.

    • Kirstie M. Bertram
    • , Rachel A. Botting
    •  & Andrew N. Harman

  • Article
    | Open Access

    Here, Frisbee et al. show that hypervirulent Clostridium difficile induces IL-33 expression in the gut and IL-33 reduces mortality and morbidity via group 2 innate lymphoid cells. Furthermore, serum levels of the soluble IL-33 decoy receptor, sST2, are associated with enhanced disease severity in human C. difficile patients.

    • Alyse L. Frisbee
    • , Mahmoud M. Saleh
    •  & William A. Petri Jr.

  • Article
    | Open Access

    Microbiota impacts all major aspects of physiology, but little is known about its effects on age-related changes in immune responses. Here the authors show that gut microbiota transfer between adult and old mice increases local but not systemic germinal centre responses regardless of age directionality.

    • Marisa Stebegg
    • , Alyssa Silva-Cayetano
    •  & Michelle A. Linterman

  • Article
    | Open Access

    Gut lumen antigens must be continuously sampled by the immune system to maintain proper immune homeostasis. Here the authors show that activated CCR6+CCR1+GL7- gut B cells retrieve lumen antigens from specialized M cells and transfer them across the subepithelial dome in the Peyer’s patch to contribute to the maintenance of gut humoral immunity.

    • Rathan Joy Komban
    • , Anneli Strömberg
    •  & Nils Lycke

  • Article
    | Open Access

    Schistosoma mansoniinfection has been linked with an increased risk of HIV acquisition in women. Here, the authors show that standard S. mansoniinfection treatment causes a reduction of HIV entry into cervical and blood CD4+ T cells, which is sustained for up to two months and is associated with de-repression of IFN-I signaling. 

    • Sergey Yegorov
    • , Vineet Joag
    •  & Rupert Kaul

  • Article
    | Open Access

    Mucosal-associated invariant T (MAIT) cells express invariant TRAV1/TRAJ33 TCR-α gene segments and detect antigens presented by MR1. Here the authors show that atypical, MR1-restricted MAIT populations that include both Trav1+ and Trav1- cells are found in both Traj33-deficient mice and human peripheral blood.

    • Hui-Fern Koay
    • , Nicholas A. Gherardin
    •  & Dale I. Godfrey

  • Article
    | Open Access

    Respiratory syncytial virus (RSV) can trigger secondary airway bacterial infections. Here, by proteomics and metagenomics analyses of samples from Kenyan children, the authors report that RSV associates with Streptococcus burden and a local upper airway response with direct antibacterial properties.

    • Charles J. Sande
    • , James M. Njunge
    •  & Andrew J. Pollard

  • Article
    | Open Access

    The authors show that the CD200 receptor (CD200R) promotes effective clearance of pulmonary Francisella tularensis infection in knock out mice. This result is unexpected as CD200R is known to dampen pulmonary immune responses, and these data suggest that the beneficial effect against F. tularensis is due to depletion of a neutrophil niche for the bacterium.

    • J. Casulli
    • , M. E. Fife
    •  & M. A Travis

  • Article
    | Open Access

    Innate lymphoid cells (ILC), including natural killer (NK) cells, are important innate immune regulators. Here the authors show that, in human infant intestines, CD103+Eomes+ NK cells are the predominant ILC population, but are replaced gradually by Eomes+ T cells, while NKp44+ NK cells persist in adult intestines.

    • Adrian F. Sagebiel
    • , Fenja Steinert
    •  & Madeleine J. Bunders

  • Article
    | Open Access

    Oral vaccination is a potential option to elicit systemic and mucosal immunity against HIV. Here, Jones et al. show that oral vaccination with a modified needle-free injector induces protective immunity against SHIV in non-human primates and is superior to topical application of vaccines to oral tissues.

    • Andrew T. Jones
    • , Xiaoying Shen
    •  & Rama Rao Amara

  • 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

    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

    The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.

    • Laura A. Hancock
    • , Corinne E. Hennessy
    •  & David A. Schwartz

  • Article
    | Open Access

    Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

    • Claudia Burrello
    • , Federica Garavaglia
    •  & Federica Facciotti

  • Article
    | Open Access

    Hepatitis E virus (HEV) infection can result in severe placental disease, but mechanisms underlying pathogenicity are poorly understood. Here, the authors develop an ex vivo model for HEV infection at the maternal-fetal interface and compare pathogenicity of different HEV genotypes.

    • Jordi Gouilly
    • , Qian Chen
    •  & Hicham El Costa

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