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Interferon-induced guanylate-binding proteins in inflammasome activation and host defense

Nature Immunology volume 17, pages 481–489 (2016)Cite this article

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Abstract

Traditional views of the inflammasome highlight the assembly of pre-existing core components shortly after infection or tissue damage. Emerging work, however, suggests that the inflammasome machinery is also subject to 'tunable' or inducible signals that might accelerate its autocatalytic properties and dictate where inflammasome assembly takes place in the cell. Many of these signals operate downstream of interferon receptors to elicit inflammasome regulators, including a new family of interferon-induced GTPases called 'guanylate-binding proteins' (GBPs). Here we investigate the critical roles of interferon-induced GBPs in directing inflammasome subtype–specific responses and their consequences for cell-autonomous immunity to a wide variety of microbial pathogens. We discuss emerging mechanisms of action and the potential effect of these GBPs on predisposition to sepsis and other infectious or inflammatory diseases.

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Figure 1: Evolutionary links between GBPs and the inflammasome machinery gleaned from fossil-record studies.
Figure 2: Familial and structural properties of the GBPs.
Figure 3: Specific steps at which individual GBPs affect canonical versus non-canonical inflammasome cascades.
Figure 4: Molecular mechanisms of GBPs in inflammasome activation.

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References

  1. Daugherty, M.D. & Malik, H.S. Rules of engagement: molecular insights from host-virus arms races. Annu. Rev. Genet. 46, 677–700 (2012).

    Article  CAS  PubMed  Google Scholar 

  2. Aravind, L., Dixit, V.M. & Koonin, E.V. Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291, 1279–1284 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. MacMicking, J.D. Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat. Rev. Immunol. 12, 367–382 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lamkanfi, M. & Dixit, V.M. Mechanisms and functions of inflammasomes. Cell 157, 1013–1022 (2014).

    Article  CAS  PubMed  Google Scholar 

  5. Angosto, D. et al. Evolution of inflammasome functions in vertebrates: Inflammasome and caspase-1 trigger fish macrophage cell death but are dispensable for the processing of IL-1β. Innate Immun. 18, 815–824 (2012).

    Article  PubMed  CAS  Google Scholar 

  6. Henry, T., Brotcke, A., Weiss, D.S., Thompson, L.J. & Monack, D.M. Type I interferon signaling is required for activation of the inflammasome during Francisella infection. J. Exp. Med. 204, 987–994 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jones, J.W. et al. Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proc. Natl. Acad. Sci. USA 107, 9771–9776 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rathinam, V.A. et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395–402 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dombrowski, Y. et al. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl. Med. 3, 82ra38 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Kerur, N. et al. IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi sarcoma-associated herpesvirus infection. Cell Host Microbe 9, 363–375 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rathinam, V.A. et al. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria. Cell 150, 606–619 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shenoy, A.R. et al. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science 336, 481–485 (2012).

    Article  CAS  PubMed  Google Scholar 

  13. Aachoui, Y. et al. Caspase-11 protects against bacteria that escape the vacuole. Science 339, 975–978 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Case, C.L. et al. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. Proc. Natl. Acad. Sci. USA 110, 1851–1856 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hagar, J.A., Powell, D.A., Aachoui, Y., Ernst, R.K. & Miao, E.A. Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic shock. Science 341, 1250–1253 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Strittmatter, G.E. et al. IFN-γ primes keratinocytes for HSV-1-induced inflammasome activation. J. Invest. Dermatol. 136, 610–620 (2016).

    Article  CAS  PubMed  Google Scholar 

  17. Pilla, D.M. et al. Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. Proc. Natl. Acad. Sci. USA 111, 6046–6051 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Meunier, E. et al. Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases. Nature 509, 366–370 (2014).

    Article  CAS  PubMed  Google Scholar 

  19. Aachoui, Y. et al. Canonical inflammasomes drive IFN-γ to prime caspase-11 in defense against a cytosol-invasive bacterium. Cell Host Microbe 18, 320–332 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Finethy, R. et al. Guanylate binding proteins enable rapid activation of canonical and noncanonical inflammasomes in chlamydia-infected macrophages. Infect. Immun. 83, 4740–4749 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).

    Article  CAS  PubMed  Google Scholar 

  22. Man, S.M. et al. The transcription factor IRF1 and guanylate-binding proteins target activation of the AIM2 inflammasome by Francisella infection. Nat. Immunol. 16, 467–475 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Meunier, E. et al. Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida. Nat. Immunol. 16, 476–484 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim, B.H., Shenoy, A.R., Kumar, P., Bradfield, C.J. & MacMicking, J.D. IFN-inducible GTPases in host cell defense. Cell Host Microbe 12, 432–444 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Latz, E., Xiao, T.S. & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397–411 (2013).

    Article  CAS  PubMed  Google Scholar 

  26. von Moltke, J., Ayres, J.S., Kofoed, E.M., Chavarría-Smith, J. & Vance, R.E. Recognition of bacteria by inflammasomes. Annu. Rev. Immunol. 31, 73–106 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. Chen, K.W. et al. The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge. Cell Rep. 8, 570–582 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Knodler, L.A. et al. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 16, 249–256 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. Kayagaki, N. et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341, 1246–1249 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Shi, J. et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514, 187–192 (2014).

    Article  CAS  PubMed  Google Scholar 

  32. Casson, C.N. et al. Human caspase-4 mediates noncanonical inflammasome activation against Gram-negative bacterial pathogens. Proc. Natl. Acad. Sci. USA 112, 6688–6693 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Broz, P., von Moltke, J., Jones, J.W., Vance, R.E. & Monack, D.M. Differential requirement for caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing. Cell Host Microbe 8, 471–483 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Broz, P. et al. Caspase-11 increases susceptibility to salmonella infection in the absence of caspase-1. Nature 490, 288–291 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lu, A. et al. Unified polymerization mechanism for the assembly of ASC-dependent inflammasomes. Cell 156, 1193–1206 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cai, X. et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell 156, 1207–1222 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hu, Z. et al. Structural and biochemical basis for induced self-propagation of NLRC4. Science 350, 399–404 (2015).

    Article  CAS  PubMed  Google Scholar 

  38. Zhang, L. et al. Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization. Science 350, 404–409 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fernandes-Alnemri, T., Yu, J.W., Datta, P., Wu, J. & Alnemri, E.S. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509–513 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hornung, V. et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514–518 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Muñoz-Planillo, R. et al. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity 38, 1142–1153 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Guarda, G. et al. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity 34, 213–223 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Franchi, L., Eigenbrod, T. & Núñez, G. Cutting edge: TNF-α mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J. Immunol. 183, 792–796 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Lee, C.K., Smith, E., Gimeno, R., Gertner, R. & Levy, D.E. STAT1 affects lymphocyte survival and proliferation partially independent of its role downstream of IFN-γ. J. Immunol. 164, 1286–1292 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Schauvliege, R., Vanrobaeys, J., Schotte, P. & Beyaert, R. Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-κB and signal transducer and activator of transcription (STAT) 1. J. Biol. Chem. 277, 41624–41630 (2002).

    Article  CAS  PubMed  Google Scholar 

  46. Lu, B. et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature 488, 670–674 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. He, Y., Franchi, L. & Núñez, G. The protein kinase PKR is critical for LPS-induced iNOS production but dispensable for inflammasome activation in macrophages. Eur. J. Immunol. 43, 1147–1152 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hett, E.C. et al. Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis. Nat. Chem. Biol. 9, 398–405 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim, B.H. et al. A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection. Science 332, 717–721 (2011).

    Article  CAS  PubMed  Google Scholar 

  50. Jin, T., Huang, M., Smith, P., Jiang, J. & Xiao, T.S. Structure of the caspase-recruitment domain from a zebrafish guanylate-binding protein. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 69, 855–860 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Olszewski, M.A., Gray, J. & Vestal, D.J. In silico genomic analysis of the human and murine guanylate-binding protein (GBP) gene clusters. J. Interferon Cytokine Res. 26, 328–352 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Degrandi, D. et al. Extensive characterization of IFN-induced GTPases mGBP1 to mGBP10 involved in host defense. J. Immunol. 179, 7729–7740 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Shenoy, A.R. et al. Emerging themes in IFN-γ-induced macrophage immunity by the p47 and p65 GTPase families. Immunobiology 212, 771–784 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. MacMicking, J.D., Taylor, G.A. & McKinney, J.D. Immune control of tuberculosis by IFN-γ-inducible LRG-47. Science 302, 654–659 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Martens, S. et al. Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLoS Pathog. 1, e24 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Staeheli, P., Prochazka, M., Steigmeier, P.A. & Haller, O. Genetic control of interferon action: mouse strain distribution and inheritance of an induced protein with guanylate-binding property. Virology 137, 135–142 (1984).

    Article  CAS  PubMed  Google Scholar 

  57. Kim, S. et al. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur. J. Immunol. 40, 1545–1551 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rupper, A.C. & Cardelli, J.A. Induction of guanylate binding protein 5 by γ interferon increases susceptibility to Salmonella enterica serovar Typhimurium-induced pyroptosis in RAW 264.7 cells. Infect. Immun. 76, 2304–2315 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Marty-Roix, R. et al. Identification of QS-21 as an inflammasome-activating molecular component of saponin adjuvants. J. Biol. Chem. 291, 1123–1136 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9, 847–856 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sheedy, F.J. et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14, 812–820 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Okada, M., Matsuzawa, A., Yoshimura, A. & Ichijo, H. The lysosome rupture-activated TAK1-JNK pathway regulates NLRP3 inflammasome activation. J. Biol. Chem. 289, 32926–32936 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Randow, F., MacMicking, J.D. & James, L.C. Cellular self-defense: how cell-autonomous immunity protects against pathogens. Science 340, 701–706 (2013).

    Article  CAS  PubMed  Google Scholar 

  64. Pierini, R. et al. ASC controls IFN-γ levels in an IL-18-dependent manner in caspase-1-deficient mice infected with Francisella novicida. J. Immunol. 191, 3847–3857 (2013).

    Article  CAS  PubMed  Google Scholar 

  65. Yamamoto, M. et al. A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii. Immunity 37, 302–313 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Wehner, M. & Herrmann, C. Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant. FEBS J. 277, 1597–1605 (2010).

    Article  CAS  PubMed  Google Scholar 

  67. Ghosh, A., Praefcke, G.J., Renault, L., Wittinghofer, A. & Herrmann, C. How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature 440, 101–104 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Syguda, A. et al. Tetramerization of human guanylate-binding protein 1 is mediated by coiled-coil formation of the C-terminal α-helices. FEBS J. 279, 2544–2554 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Abdullah, N., Srinivasan, B., Modiano, N., Cresswell, P. & Sau, A.K. Role of individual domains and identification of internal gap in human guanylate binding protein-1. J. Mol. Biol. 386, 690–703 (2009).

    Article  CAS  PubMed  Google Scholar 

  70. Britzen-Laurent, N. et al. Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner. PLoS One 5, e14246 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Degrandi, D. et al. Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication. Proc. Natl. Acad. Sci. USA 110, 294–299 (2013).

    Article  CAS  PubMed  Google Scholar 

  72. Selleck, E.M. et al. Guanylate-binding protein 1 (Gbp1) contributes to cell-autonomous immunity against Toxoplasma gondii. PLoS Pathog. 9, e1003320 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tietzel, I., El-Haibi, C. & Carabeo, R.A. Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-γ. PLoS One 4, e6499 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Virreira Winter, S. et al. Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS One 6, e24434 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Lee, Y. et al. p62 plays a specific role in interferon-γ-induced presentation of a toxoplasma vacuolar antigen. Cell Rep. 13, 223–233 (2015).

    Article  CAS  PubMed  Google Scholar 

  76. Niedelman, W., Sprokholt, J.K., Clough, B., Frickel, E.M. & Saeij, J.P. Cell death of γ interferon-stimulated human fibroblasts upon Toxoplasma gondii infection induces early parasite egress and limits parasite replication. Infect. Immun. 81, 4341–4349 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ohshima, J. et al. Role of mouse and human autophagy proteins in IFN-γ-induced cell-autonomous responses against Toxoplasma gondii. J. Immunol. 192, 3328–3335 (2014).

    Article  CAS  PubMed  Google Scholar 

  78. Selleck, E.M. et al. A noncanonical autophagy pathway restricts Toxoplasma gondii growth in a strain-specific manner in IFN-γ-activated human cells. MBio 6, e01157–e15 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kagan, J.C., Magupalli, V.G. & Wu, H. SMOCs: supramolecular organizing centres that control innate immunity. Nat. Rev. Immunol. 14, 821–826 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kravets, E. et al. The GTPase activity of murine guanylate-binding protein 2 (mGBP2) controls the intracellular localization and recruitment to the parasitophorous vacuole of Toxoplasma gondii. J. Biol. Chem. 287, 27452–27466 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).

    Article  CAS  PubMed  Google Scholar 

  82. MacMicking, J.D. IFN-inducible GTPases and immunity to intracellular pathogens. Trends Immunol. 25, 601–609 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Tiwari, S., Choi, H.P., Matsuzawa, T., Pypaert, M. & MacMicking, J.D. Targeting of the GTPase Irgm1 to the phagosomal membrane via PtdIns(3,4)P2 and PtdIns(3,4,5)P3 promotes immunity to mycobacteria. Nat. Immunol. 10, 907–917 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Haldar, A.K. et al. IRG and GBP host resistance factors target aberrant, “non-self” vacuoles characterized by the missing of “self” IRGM proteins. PLoS Pathog. 9, e1003414 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ohtsuka, S. et al. SQSTM1/p62/A170 regulates the severity of Legionella pneumophila pneumonia by modulating inflammasome activity. Eur. J. Immunol. 44, 1084–1092 (2014).

    Article  CAS  PubMed  Google Scholar 

  86. Haldar, A.K. et al. Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins. Proc. Natl. Acad. Sci. USA 112, E5628–E5637 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Hotchkiss, R.S., Monneret, G. & Payen, D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol. 13, 862–874 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. MacMicking, J.D. et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81, 641–650 (1995).

    Article  CAS  PubMed  Google Scholar 

  89. Döcke, W.D. et al. Monocyte deactivation in septic patients: restoration by IFN-γ treatment. Nat. Med. 3, 678–681 (1997).

    Article  PubMed  Google Scholar 

  90. Broderick, L., De Nardo, D., Franklin, B.S., Hoffman, H.M. & Latz, E. The inflammasomes and autoinflammatory syndromes. Annu. Rev. Pathol. 10, 395–424 (2015).

    Article  CAS  PubMed  Google Scholar 

  91. Crow, Y.J. & Manel, N. Aicardi-Goutières syndrome and the type I interferonopathies. Nat. Rev. Immunol. 15, 429–440 (2015).

    Article  CAS  PubMed  Google Scholar 

  92. Jeremiah, N. et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J. Clin. Invest. 124, 5516–5520 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Supported by the HHMI Investigator Program, NIH NIAID (R01 AI068041-10 and R01 AI108834-02), the American Asthma Foundation Research Program (14-0073) and the Rainin Foundation (14H7).

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

    Bae-Hoon Kim & John D MacMicking

  2. Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA

    Bae-Hoon Kim, Jonathan D Chee, Clinton J Bradfield, Eui-Soon Park, Pradeep Kumar & John D MacMicking

  3. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    John D MacMicking

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Kim, BH., Chee, J., Bradfield, C. et al. Interferon-induced guanylate-binding proteins in inflammasome activation and host defense. Nat Immunol 17, 481–489 (2016). https://doi.org/10.1038/ni.3440

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