Mucosal immunology

  • Article
    | Open Access

    There has been limited research on the role of the mucosal immune response to SARS-CoV-2 infection. Here, the authors perform a prospective observational household study and find that mucosal antibody responses are associated with decreased viral load and faster resolution of systemic symptoms.

    • Janeri Fröberg
    • , Joshua Gillard
    •  & Dimitri A. Diavatopoulos
  • Article
    | Open Access

    Anti-retroviral treatment does not fully resolve mucosal dysfunction and systemic inflammation in HIV infected individuals. Authors show here that an unusual population of regulatory T cells, distinguished by Amphiregulin expression and the incapability to suppress CD4 T cells might contribute to disrupted oral immune protection in HIV patients.

    • N. Bhaskaran
    • , E. Schneider
    •  & P. Pandiyan
  • Article
    | Open Access

    Influenza infection during pregnancy can affect health of offspring but it is not clear how this affects immune responses. Here the authors use a mouse model to show that influenza infection during pregnancy can increase susceptibility to secondary infection and alter immune cell function in offspring.

    • Henning Jacobsen
    • , Kerstin Walendy-Gnirß
    •  & Gülsah Gabriel
  • Article
    | Open Access

    Dendritic cells initiate and regulate adaptive immunity and differ according to gut anatomical location. Here the authors show that DC residing in the upper and lower intestines show differential PD-L1 and XCR1 expression and drive specific T cell responses to prevent gut inflammation.

    • Thais G. Moreira
    • , Davide Mangani
    •  & Howard L. Weiner
  • Article
    | Open Access

    Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-γ transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy.

    • Emma V. Petley
    • , Hui-Fern Koay
    •  & Phillip K. Darcy
  • Article
    | Open Access

    Intraepithelial lymphocytes (IEL) respond to IL-15 complexed with IL-15Ra but how this intrinsically affects IEL is unclear. Here the authors use proteomics analyses of the main mouse IEL subsets and identify PIM kinases as essential for IEL proliferation, metabolism and effector function downstream of IL-15.

    • Olivia J. James
    • , Maud Vandereyken
    •  & Mahima Swamy
  • Article
    | Open Access

    Lung resident memory T (TRM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung TRM cells that might be important to limit reinfection.

    • Judith Grau-Expósito
    • , Nerea Sánchez-Gaona
    •  & Meritxell Genescà
  • Article
    | Open Access

    Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.

    • Constance McElrath
    • , Vanessa Espinosa
    •  & Sergei V. Kotenko
  • Review Article
    | Open Access

    At the centre of intestinal health and the fight against obesity and metabolic syndrome is the intestinal microbiota and its interaction with our immune systems. Here the authors Review the current understanding of how these systems interact and how we can capitalize on recent advances to provide better therapeutic options.

    • Saad Khan
    • , Helen Luck
    •  & Daniel A. Winer
  • Article
    | Open Access

    Crohn’s disease results from transmural inflammation in the gut, but analyses of local immune populations are still lacking. Here, the authors show, by combining multiple single-cell approaches, that intraepithelial and lamina propria T cells are heterogenous, show unique phenotypes, and exhibit altered subsets upon inflammation.

    • Natalia Jaeger
    • , Ramya Gamini
    •  & Marco Colonna
  • Article
    | Open Access

    The pandemic of COVID-19, caused by SARS-CoV-2 infection, warrants immediate investigation for therapy options. Here the authors show, using epithelial and air-liquid interface cultures, that SARS-CoV-2 hijacks host cell metabolism to facilitate viral replication, and that inhibition of mTORC1, a master metabolic regulator, suppresses viral replication.

    • Peter J. Mullen
    • , Gustavo Garcia Jr
    •  & Heather R. Christofk
  • Article
    | Open Access

    Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.

    • Benjamin A. H. Jensen
    • , Jacob B. Holm
    •  & Tor E. Lea
  • Article
    | Open Access

    Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn’s disease. Here, the authors show pancreatic GP-2 is the source of the intestine’s luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model.

    • Yosuke Kurashima
    • , Takaaki Kigoshi
    •  & Hiroshi Kiyono
  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is a disease of prematurity requiring Toll-like receptor 4 (TLR4) activation on the gut epithelium. Here the authors show that the aryl hydrocarbon receptor (AHR) mediates NEC pathogenesis via effects on TLR4, and that supplementing the diet with AHR ligands during pregnancy or postnatally prevents NEC.

    • Peng Lu
    • , Yukihiro Yamaguchi
    •  & David J. Hackam
  • Article
    | Open Access

    Transfer of a host’s microbiota by faecal microbiota transplantation has shown benefit in the context of recurrent Clostridioides difficle infection. Here the authors shows the inflammatory status of the recipient can impact on engraftment and the efficacy of the introduced microbiota in a model of C.difficile infection.

    • Eric R. Littmann
    • , Jung-Jin Lee
    •  & Michael C. Abt
  • 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.