Science immunology

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ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways
Science immunology - Tập 1 Số 2 - 2016
Teneema Kuriakose, Si Ming Man, R. K. Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E. Place, Geoffrey Neale, Peter Vogel, Thirumala‐Devi Kanneganti

ZBP1 activates the NLRP3 inflammasome and programmed cell death.

Neutrophil extracellular traps drive inflammatory pathogenesis in malaria
Science immunology - Tập 4 Số 40 - 2019
Sebastian Lorenz Knackstedt, Athina Georgiadou, Falko Apel, Ulrike Abu-Abed, Christopher A. Moxon, Aubrey J. Cunnington, Bärbel Raupach, Deirdre Cunningham, Jean Langhorne, Renate Krüger, Valentina Barrera, Simon Harding, Åse Berg, Sam Patel, Kari Otterdal, Benjamin Mordmüller, Evelin Schwarzer, Volker Brinkmann, Arturo Zychlinsky, Borko Amulic

NETs contribute to malaria by promoting emergency granulopoiesis and endothelial binding of parasitized erythrocytes.

Gasdermin D plays a vital role in the generation of neutrophil extracellular traps
Science immunology - Tập 3 Số 26 - 2018
Gabriel Sollberger, Axel Choidas, Garth L. Burn, Peter Habenberger, Raffaella Di Lucrezia, Susanne Kordes, Sascha Menninger, Jan Eickhoff, Peter Nußbaumer, Bert Klebl, Renate Krüger, Alf Herzig, Arturo Zychlinsky

By screening a library of compounds that block NETosis, we have identified a gasdermin D inhibitor.

Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters
Science immunology - Tập 7 Số 69 - 2022
Maryam Keshavarz, Schayan Faraj Tabrizi, Anna-Lena Ruppert, Uwe Pfeil, Yannick Schreiber, Jochen Klein, Isabell Brandenburger, Günter Lochnit, Sudhanshu Bhushan, Alexander Perniss, Klaus Deckmann, Petra Hartmann, Mirjam Meiners, Petra Mermer, Muhammad Rafiq, Sarah Winterberg, Tamara Papadakis, Dominique Thomas, Carlo Angioni, Johannes Oberwinkler, Vladimir Chubanov, Thomas Gudermann, Ulrich Gärtner, Stefan Offermanns, Burkhard Schütz, Wolfgang Kummer

The gallbladder stores bile between meals and empties into the duodenum upon demand and is thereby exposed to the intestinal microbiome. This exposure raises the need for antimicrobial factors, among them, mucins produced by cholangiocytes, the dominant epithelial cell type in the gallbladder. The role of the much less frequent biliary tuft cells is still unknown. We here show that propionate, a major metabolite of intestinal bacteria, activates tuft cells via the short-chain free fatty acid receptor 2 and downstream signaling involving the cation channel transient receptor potential cation channel subfamily M member 5. This results in corelease of acetylcholine and cysteinyl leukotrienes from tuft cells and evokes synergistic paracrine effects upon the epithelium and the gallbladder smooth muscle, respectively. Acetylcholine triggers mucin release from cholangiocytes, an epithelial defense mechanism, through the muscarinic acetylcholine receptor M3. Cysteinyl leukotrienes cause gallbladder contraction through their cognate receptor CysLTR1, prompting emptying and closing. Our results establish gallbladder tuft cells as sensors of the microbial metabolite propionate, initiating dichotomous innate defense mechanisms through simultaneous release of acetylcholine and cysteinyl leukotrienes.

BMP signaling in the intestinal epithelium drives a critical feedback loop to restrain IL-13–driven tuft cell hyperplasia
Science immunology - Tập 7 Số 71 - 2022
Håvard T. Lindholm, N. Parmar, Claire Drurey, Marta Campillo Poveda, Pia M. Vornewald, Jenny Ostrop, Alberto Díez-Sánchez, Rick M. Maizels, Menno J. Oudhoff

The intestinal tract is a common site for various types of infections including viruses, bacteria, and helminths, each requiring specific modes of immune defense. The intestinal epithelium has a pivotal role in both immune initiation and effector stages, which are coordinated by lymphocyte cytokines such as IFNγ, IL-13, and IL-22. Here, we studied intestinal epithelial immune responses using organoid image analysis based on a convolutional neural network, transcriptomic analysis, and in vivo infection models. We found that IL-13 and IL-22 both induce genes associated with goblet cells, but the resulting goblet cell phenotypes are dichotomous. Moreover, only IL-13–driven goblet cells are associated with classical NOTCH signaling. We further showed that IL-13 induces the bone morphogenetic protein (BMP) pathway, which acts in a negative feedback loop on immune type 2–driven tuft cell hyperplasia. This is associated with inhibiting Sox4 expression to putatively limit the tuft cell progenitor population. Blocking ALK2, a BMP receptor, with the inhibitor dorsomorphin homolog 1 (DMH1) interrupted the feedback loop, resulting in greater tuft cell numbers both in vitro and in vivo after infection with Nippostrongylus brasiliensis . Together, this investigation of cytokine effector responses revealed an unexpected and critical role for the BMP pathway in regulating type 2 immunity, which can be exploited to tailor epithelial immune responses.

Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Science immunology - Tập 4 Số 41 - 2019
Emily L. Goldberg, Ryan D. Molony, Eriko Kudo, Sviatoslav Sidorov, Yong Kong, Vishwa Deep Dixit, Akiko Iwasaki

Ketogenic diet protects mice against influenza virus infection through γδ T cell expansion and metabolic adaptation.

M2-like, dermal macrophages are maintained via IL-4/CCL24–mediated cooperative interaction with eosinophils in cutaneous leishmaniasis
Science immunology - Tập 5 Số 46 - 2020
Sang Hun Lee, Mariana M. Chaves, Olena Kamenyeva, Pedro Henrique Gazzinelli-Guimarães, Byunghyun Kang, Gabriela Pessenda, Katiuska Passelli, Fabienne Tacchini‐Cottier, Juraj Kabát, Elizabeth A. Jacobsen, Thomas B. Nutman, David L. Sacks

IL-4/CCL24–mediated interaction with eosinophils maintains dermis-resident macrophages as replicative niches for Leishmania major .

Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response to Mycobacterium tuberculosis in vivo
Science immunology - Tập 4 Số 37 - 2019
Alissa C. Rothchild, Gregory S. Olson, Johannes Nemeth, Lynn M. Amon, Dat Mai, Elizabeth S. Gold, Alan H. Diercks, Alan Aderem

Induction of an NRF2-dependent cell-protective signature impairs alveolar macrophages from controlling M.tb. infection in vivo.

Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria
Science immunology - Tập 2 Số 18 - 2017
Kathryn A. Knoop, Jenny Gustafsson, Keely G. McDonald, Devesha H. Kulkarni, Paige E. Coughlin, Stephanie McCrate, Dongyeon Kim, Chyi‐Song Hsieh, Simon P. Hogan, Charles O. Elson, Phillip I. Tarr, Rodney D. Newberry

Bacterial antigen encounter in a preweaning interval is critical for developing antigen-specific tolerance to gut bacteria.

Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct
Science immunology - Tập 7 Số 75 - 2022
Anna Z. Mykytyn, Melanie Rissmann, Adinda Kok, Miruna E. Rosu, Debby Schipper, Tim I. Breugem, Petra B. van den Doel, Felicity Chandler, Theo M. Bestebroer, Maurice de Wit, Martin E. van Royen, Richard Molenkamp, Bas B. Oude Munnink, Rory D. de Vries, Corine H. GeurtsvanKessel, Derek J. Smith, Marion Koopmans, Barry Rockx, Mart M. Lamers, Ron A. M. Fouchier, Bart L. Haagmans

The emergence and rapid spread of SARS-CoV-2 variants may affect vaccine efficacy substantially. The Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed. Here, we used antigenic cartography to quantify and visualize antigenic differences between early SARS-CoV-2 variants (614G, Alpha, Beta, Gamma, Zeta, Delta, and Mu) using hamster antisera obtained after primary infection. We first verified that the choice of the cell line for the neutralization assay did not affect the topology of the map substantially. Antigenic maps generated using pseudo-typed SARS-CoV-2 on the widely used VeroE6 cell line and the human airway cell line Calu-3 generated similar maps. Maps made using authentic SARS-CoV-2 on Calu-3 cells also closely resembled those generated with pseudo-typed viruses. The antigenic maps revealed a central cluster of SARS-CoV-2 variants, which grouped on the basis of mutual spike mutations. Whereas these early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape vaccine-induced antibody responses as a result of different antigenic characteristics. Thus, antigenic cartography could be used to assess antigenic properties of future SARS-CoV-2 variants of concern that emerge and to decide on the composition of novel spike-based (booster) vaccines.

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