Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.

Abstract:

:Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding proteins (GBPs) assemble on the surface of Gram-negative bacteria into polyvalent signaling platforms required for activation of caspase-4. Caspase-4 activation is hierarchically controlled by GBPs; GBP1 initiates platform assembly, GBP2 and GBP4 control caspase-4 recruitment, and GBP3 governs caspase-4 activation. In response to cytosol-invading bacteria, activation of caspase-4 through the GBP platform is essential to induce gasdermin-D-dependent pyroptosis and processing of interleukin-18, thereby destroying the replicative niche for intracellular bacteria and alerting neighboring cells, respectively. Caspase-11 and GBPs epistatically protect mice against lethal bacterial challenge. Multiple antagonists of the pathway encoded by Shigella flexneri, a cytosol-adapted bacterium, provide compelling evolutionary evidence for the importance of the GBP-caspase-4 pathway in antibacterial defense.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Wandel MP,Kim BH,Park ES,Boyle KB,Nayak K,Lagrange B,Herod A,Henry T,Zilbauer M,Rohde J,MacMicking JD,Randow F

doi

10.1038/s41590-020-0697-2

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

880-891

issue

8

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-020-0697-2

journal_volume

21

pub_type

杂志文章
  • Production of Ins(1,3,4,5)P4 mediated by the kinase Itpkb inhibits store-operated calcium channels and regulates B cell selection and activation.

    abstract::Antigen receptor-mediated production of inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) in lymphocytes triggers the release of Ca2+ from intracellular stores; this release of Ca2+ results in the opening of store-operated Ca2+ channels in the plasma membrane. Here we report that mice lacking Ins(1,4,5)P3 3-kinase B (Itpkb)...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1458

    authors: Miller AT,Sandberg M,Huang YH,Young M,Sutton S,Sauer K,Cooke MP

    更新日期:2007-05-01 00:00:00

  • Autophagy and autophagy-related proteins in the immune system.

    abstract::Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In add...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.3273

    authors: Shibutani ST,Saitoh T,Nowag H,Münz C,Yoshimori T

    更新日期:2015-10-01 00:00:00

  • Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.

    abstract::Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis. Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Fas kills activated primary T cells efficiently in the absence of active ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/82732

    authors: Holler N,Zaru R,Micheau O,Thome M,Attinger A,Valitutti S,Bodmer JL,Schneider P,Seed B,Tschopp J

    更新日期:2000-12-01 00:00:00

  • Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells.

    abstract::Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during ly...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1695

    authors: Guimond M,Veenstra RG,Grindler DJ,Zhang H,Cui Y,Murphy RD,Kim SY,Na R,Hennighausen L,Kurtulus S,Erman B,Matzinger P,Merchant MS,Mackall CL

    更新日期:2009-02-01 00:00:00

  • The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes.

    abstract::The CD4 versus CD8 lineage specification of thymocytes is linked to coreceptor expression. The transcription factor MAZR has been identified as an important regulator of Cd8 expression. Here we show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR ne...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1860

    authors: Sakaguchi S,Hombauer M,Bilic I,Naoe Y,Schebesta A,Taniuchi I,Ellmeier W

    更新日期:2010-05-01 00:00:00

  • Publisher Correction: SERPINB1-mediated checkpoint of inflammatory caspase activation.

    abstract::In the version of this article initially published, the label (CASP4-C285A-HA) above the second and fifth lanes in the right blot in Fig. 1e is incorrect; the correct label is CASP4-C258A-HA. Also, the two labels at right above the plot in Fig. 6c were switched; the far right label should be 'Co-housed Serpinb1a-/-' (...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-019-0361-x

    authors: Choi YJ,Kim S,Choi Y,Nielsen TB,Yan J,Lu A,Ruan J,Lee HR,Wu H,Spellberg B,Jung JU

    更新日期:2019-05-01 00:00:00

  • Neutrophil direction sensing and superoxide production linked by the GTPase-activating protein GIT2.

    abstract::In neutrophils, superoxide anion production generally accompanies chemotaxis and functions in killing invading pathogens. The GIT2 GTPase-activating protein binds to the guanine nucleotide-exchange factor alphaPIX. Here we show that GIT2 was necessary for directional chemotaxis and for the suppression of superoxide pr...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1349

    authors: Mazaki Y,Hashimoto S,Tsujimura T,Morishige M,Hashimoto A,Aritake K,Yamada A,Nam JM,Kiyonari H,Nakao K,Sabe H

    更新日期:2006-07-01 00:00:00

  • An innate antiviral pathway acting before interferons at epithelial surfaces.

    abstract::Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3319

    authors: Iversen MB,Reinert LS,Thomsen MK,Bagdonaite I,Nandakumar R,Cheshenko N,Prabakaran T,Vakhrushev SY,Krzyzowska M,Kratholm SK,Ruiz-Perez F,Petersen SV,Goriely S,Bibby BM,Eriksson K,Ruland J,Thomsen AR,Herold BC,Wandall H

    更新日期:2016-02-01 00:00:00

  • High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.

    abstract::High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, p...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2784

    authors: De Nardo D,Labzin LI,Kono H,Seki R,Schmidt SV,Beyer M,Xu D,Zimmer S,Lahrmann C,Schildberg FA,Vogelhuber J,Kraut M,Ulas T,Kerksiek A,Krebs W,Bode N,Grebe A,Fitzgerald ML,Hernandez NJ,Williams BR,Knolle P,Kneillin

    更新日期:2014-02-01 00:00:00

  • Plant NBS-LRR proteins in pathogen sensing and host defense.

    abstract::Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often t...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1410

    authors: DeYoung BJ,Innes RW

    更新日期:2006-12-01 00:00:00

  • The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity.

    abstract::Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Ele...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3385

    authors: Gonzalez-Martin A,Adams BD,Lai M,Shepherd J,Salvador-Bernaldez M,Salvador JM,Lu J,Nemazee D,Xiao C

    更新日期:2016-04-01 00:00:00

  • CCL19-CCR7-dependent reverse transendothelial migration of myeloid cells clears Chlamydia muridarum from the arterial intima.

    abstract::Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3564

    authors: Roufaiel M,Gracey E,Siu A,Zhu SN,Lau A,Ibrahim H,Althagafi M,Tai K,Hyduk SJ,Cybulsky KO,Ensan S,Li A,Besla R,Becker HM,Xiao H,Luther SA,Inman RD,Robbins CS,Jongstra-Bilen J,Cybulsky MI

    更新日期:2016-11-01 00:00:00

  • Normal T cell homeostasis: the conversion of naive cells into memory-phenotype cells.

    abstract::Weak T cell antigen receptor (TCR) signals from contact with self ligands act in synergy with antiapoptotic signals induced by interleukin 7 (IL-7) to promote the survival of naive T cells in a resting state. The amount of background TCR signaling in naive T cells is set by post-thymic TCR tuning and operates at an in...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2018

    authors: Sprent J,Surh CD

    更新日期:2011-06-01 00:00:00

  • Transcriptomic and epigenetic mechanisms underlying myeloid diversity in the lung.

    abstract::The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0582-z

    authors: Sajti E,Link VM,Ouyang Z,Spann NJ,Westin E,Romanoski CE,Fonseca GJ,Prince LS,Glass CK

    更新日期:2020-02-01 00:00:00

  • Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis.

    abstract::Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional amo...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0598-4

    authors: Weisel FJ,Mullett SJ,Elsner RA,Menk AV,Trivedi N,Luo W,Wikenheiser D,Hawse WF,Chikina M,Smita S,Conter LJ,Joachim SM,Wendell SG,Jurczak MJ,Winkler TH,Delgoffe GM,Shlomchik MJ

    更新日期:2020-03-01 00:00:00

  • Damage control: how HIV survives the editor APOBEC3G.

    abstract::The antiviral factor APOBEC3G upregulates the expression of ligands for the activating receptor NKG2D via DNA damage induced by the viral protein Vpr in cells infected with human immunodeficiency virus. The virus overcomes greater susceptibility to natural killer cell–mediated lysis by targeting APOBEC3G for degradati...

    journal_title:Nature immunology

    pub_type: 评论,新闻

    doi:10.1038/ni.2115

    authors: Croxford JL,Gasser S

    更新日期:2011-09-20 00:00:00

  • Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.

    abstract::Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2180

    authors: Butler NS,Moebius J,Pewe LL,Traore B,Doumbo OK,Tygrett LT,Waldschmidt TJ,Crompton PD,Harty JT

    更新日期:2011-12-11 00:00:00

  • Publisher Correction: Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes.

    abstract::In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Suppl...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-018-0154-7

    authors: Zhang M,Dong Y,Hu F,Yang D,Zhao Q,Lv C,Wang Y,Xia C,Weng Q,Liu X,Li C,Zhou P,Wang T,Guan Y,Guo R,Liu L,Geng Y,Wu H,Du J,Hu Z,Xu S,Chen J,He A,Liu B,Wang D,Yang YG,Wang J

    更新日期:2018-09-01 00:00:00

  • Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection.

    abstract::Despite the prevalence and clinical importance of influenza, its long-term effect on lung immunity is unclear. Here we describe that following viral clearance and clinical recovery, at 1 month after infection with influenza, mice are better protected from Streptococcus pneumoniae infection due to a population of monoc...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0568-x

    authors: Aegerter H,Kulikauskaite J,Crotta S,Patel H,Kelly G,Hessel EM,Mack M,Beinke S,Wack A

    更新日期:2020-02-01 00:00:00

  • CIRCling the wagons to protect intestinal stem cells.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 评论,杂志文章

    doi:10.1038/s41590-018-0302-0

    authors: Soveg F,von Moltke J,Savan R

    更新日期:2019-02-01 00:00:00

  • IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling.

    abstract::Mechanisms that degrade inflammatory mRNAs are well known; however, stabilizing mechanisms are poorly understood. Here, we show that Act1, an interleukin-17 (IL-17)-receptor-complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, the SEFIR-bind...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0071-9

    authors: Herjan T,Hong L,Bubenik J,Bulek K,Qian W,Liu C,Li X,Chen X,Yang H,Ouyang S,Zhou H,Zhao J,Vasu K,Cockman E,Aronica M,Asosingh K,Licatalosi DD,Qin J,Fox PL,Hamilton TA,Driscoll D,Li X

    更新日期:2018-04-01 00:00:00

  • An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide.

    abstract::EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is as...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/85266

    authors: Pedotti R,Mitchell D,Wedemeyer J,Karpuj M,Chabas D,Hattab EM,Tsai M,Galli SJ,Steinman L

    更新日期:2001-03-01 00:00:00

  • Impaired assembly of the major histocompatibility complex class I peptide-loading complex in mice deficient in the oxidoreductase ERp57.

    abstract::The thiol-oxidoreductase ERp57 is an integral component of the peptide-loading complex of the major histocompatibility complex (MHC) class I pathway, but its function is unknown. To investigate its function in antigen presentation, we generated ERp57-deficient mice. Death in utero caused by ubiquitous ERp57 deletion w...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1288

    authors: Garbi N,Tanaka S,Momburg F,Hämmerling GJ

    更新日期:2006-01-01 00:00:00

  • The crystal structure of human CD1d with and without alpha-galactosylceramide.

    abstract::The glycolipid alpha-galactosylceramide binds with high affinity to CD1d and stimulates natural killer T cells. Here we report the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 A. The structure shows a tightly fit lipid in the CD1d binding groove, with the sp...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1225

    authors: Koch M,Stronge VS,Shepherd D,Gadola SD,Mathew B,Ritter G,Fersht AR,Besra GS,Schmidt RR,Jones EY,Cerundolo V

    更新日期:2005-08-01 00:00:00

  • Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity.

    abstract::Foxp3+ regulatory T cells (Treg cells) are the central component of peripheral immune tolerance. Whereas a dysregulated Treg cytokine signature has been observed in autoimmune diseases, the regulatory mechanisms underlying pro- and anti-inflammatory cytokine production are elusive. Here, we identify an imbalance betwe...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0236-6

    authors: Sumida T,Lincoln MR,Ukeje CM,Rodriguez DM,Akazawa H,Noda T,Naito AT,Komuro I,Dominguez-Villar M,Hafler DA

    更新日期:2018-12-01 00:00:00

  • The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.

    abstract::Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter t...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1897

    authors: Kim H,Seed B

    更新日期:2010-08-01 00:00:00

  • 'Educated' dendritic cells act as messengers from memory to naive T helper cells.

    abstract::Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we fou...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1077

    authors: Alpan O,Bachelder E,Isil E,Arnheiter H,Matzinger P

    更新日期:2004-06-01 00:00:00

  • A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses.

    abstract::The family of mammalian Nod-like receptors (NLRs) consists of critical intracellular immune proteins structurally related to plant resistance proteins. The NLRs NALP3 and IPAF, for example, can each form a multiprotein proinflammatory complex called the 'inflammasome', and mutations in the gene encoding Nod2, another ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1459

    authors: Mayor A,Martinon F,De Smedt T,Pétrilli V,Tschopp J

    更新日期:2007-05-01 00:00:00

  • T cell fitness determined by signal strength.

    abstract::Two potential outcomes confront proliferating antigen-stimulated naive T cells: differentiation to effector and memory cells, or deletion. How stimulation affects cell fate is unclear. Autonomous CD8+ T cell differentiation has been proposed, but this does not explain the abortive proliferation of T cells induced by i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni908

    authors: Gett AV,Sallusto F,Lanzavecchia A,Geginat J

    更新日期:2003-04-01 00:00:00

  • Interactions of NF-kappaB with chromatin: the art of being at the right place at the right time.

    abstract::Transcription factors of the NF-kappaB family are essential regulators of the inflammatory and immune responses. The main 'switch' in NF-kappaB activation is cytoplasmic and leads to the release of NF-kappaB proteins from IkappaB molecules, specific inhibitors that prevent their nuclear accumulation. However, it is be...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1196

    authors: Natoli G,Saccani S,Bosisio D,Marazzi I

    更新日期:2005-05-01 00:00:00