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A dsRNA detector in the immune toolkit

Nod-like receptor (NLR) proteins recognize pathogen-associated molecular patterns within cells, which triggers the formation of signaling complexes called inflammasomes. These complexes then initiate pyroptosis, a highly inflammatory form of cell death. Recent work has shown that a rhinovirus protease can activate the human NLRP1 inflammasome, but it was unclear whether this is the only pathogen-derived trigger for NLRP1. Bauernfried et al. report that long, double-stranded RNA (dsRNA) generated in the course of Semliki Forest virus infection binds and activates NLRP1 in epithelial cells. dsRNA binding triggered NLRP1 to acquire adenosine triphosphatase (ATPase) activity, a common feature of activated NLR proteins. Thus, in addition to its ability to recognize viral protease activity, human NLRP1 can act as a genuine sensor of virus-associated nucleic acids.
Science, this issue p. eabd0811

Structured Abstract

INTRODUCTION

The innate immune system constitutes the first line of host defense. To detect pathogens, it uses a set of germline-encoded pattern recognition receptors (PRRs) that have evolved to sense the presence of non-self. PRRs can either directly sense pathogens or they can indirectly respond to the perturbation of cellular homeostasis during the course of pathogen infection. One group of cytosolic PRRs are inflammasome-forming nucleotide-binding domain leucine-rich repeat (NLR) proteins. After activation, they form high-molecular-weight signaling complexes that result in the direct or ASC-dependent engagement and activation of caspase-1. Active caspase-1, in turn, cleaves and thereby activates the highly proinflammatory cytokine interleukin-1β (IL-1β). In addition, caspase-1 cleaves gasdermin D (GSDMD), which results in the activation of a lytic cell death pathway known as pyroptosis. NLRP1 was one of the first inflammasome-forming PRRs to be identified, yet its role in pathogen defense in the human system remains poorly defined.

RATIONALE

NLRP1 is highly expressed and functional in epithelial barrier tissues, e.g., in keratinocytes. Unlike myeloid immune cells, keratinocytes appear to express only a limited set of inflammasome sensors, which makes them an interesting model system in which to study the role of NLRP1. To identify a potential NLRP1 stimulus, we used an immortalized keratinocyte cell line to screen a panel of viral pathogens for their potential inflammasome activation.

RESULTS

Screening different types of viruses, we found that Semliki Forest virus (SFV) triggered inflammasome activation in keratinocytes in an NLRP1-dependent fashion. As a positive-strand RNA virus, SFV generates ample amounts of double-stranded (ds) RNA during its life cycle, and the production of dsRNA coincided with the activation of NLRP1. We therefore tested poly(I:C), a synthetic dsRNA analog, and in vitro transcribed dsRNA molecules for inflammasome activation. These experiments revealed that NLRP1 was indeed stimulated by dsRNA, yet long dsRNA was required to trigger activation. These findings could be recapitulated in primary keratinocytes and immortalized bronchial epithelial cells. To determine whether this phenotype was specific for human NLRP1, we reconstituted NLRP1-deficient keratinocytes with transgenes for either human NLRP1 or murine Nlrp1b. Indeed, only keratinocytes expressing human NLRP1 were responsive to dsRNA. dsRNA-induced inflammasome activation was independent of other known dsRNA sensors, because their depletion did not decrease NLRP1 activation after dsRNA delivery. Because of these findings, we then investigated whether NLRP1 directly interacted with dsRNA. Pull-down studies revealed that human NLRP1, but not murine NLRP1B, could be immunoprecipitated by dsRNA. Using recombinant proteins, we found that NLRP1 bound nucleic acids with high affinity, predominantly through its leucine-rich repeat (LRR) domain. To ascertain whether dsRNA binding activated NLRP1 in vitro, we subsequently studied ATP hydrolysis of NLRP1 as a proxy for its activation. These studies revealed that dsRNA, but not dsDNA, triggered ATPase activity.

CONCLUSION

In 2002, human NLRP1 became the first inflammasome-forming sensor to be characterized. However, no direct ligand had been identified so far. Our work demonstrates that human NLRP1 is a bona fide nucleic acid sensor. NLRP1 directly interacts with dsRNA, a typical intermediate of viral replication, which subsequently results in the activation of the inflammasome pathway.
The pathogen-associated molecular pattern dsRNA interacts with human NLRP1 and leads to inflammasome activation.
Infection with a positive-strand RNA virus leads to the formation of dsRNA, and the generated dsRNA recruits human NLRP1. This results in the activation of NLRP1, which leads to the formation of an inflammasome complex. Inflammasome activation results in IL-1β maturation and the induction of pyroptosis.

Abstract

Inflammasomes function as intracellular sensors of pathogen infection or cellular perturbation and thereby play a central role in numerous diseases. Given the high abundance of NLRP1 in epithelial barrier tissues, we screened a diverse panel of viruses for inflammasome activation in keratinocytes. We identified Semliki Forest virus (SFV), a positive-strand RNA virus, as a potent activator of human but not murine NLRP1B. SFV replication and the associated formation of double-stranded (ds) RNA was required to engage the NLRP1 inflammasome. Moreover, delivery of long dsRNA was sufficient to trigger activation. Biochemical studies revealed that NLRP1 binds dsRNA through its leucine-rich repeat domain, resulting in its NACHT domain gaining adenosine triphosphatase activity. Altogether, these results establish human NLRP1 as a direct sensor for dsRNA and thus RNA virus infection.

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Supplementary Material

Summary

Figs. S1 to S16
Movies S1 to S12
MDAR Reproducibility Checklist

Resources

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References and Notes

1
P. Broz, V. M. Dixit, Inflammasomes: Mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16, 407–420 (2016).
2
P. Broz, P. Pelegrín, F. Shao, The gasdermins, a protein family executing cell death and inflammation. Nat. Rev. Immunol. 20, 143–157 (2020).
3
A. Liston, S. L. Masters, Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17, 208–214 (2017).
4
F. Martinon, K. Burns, J. Tschopp, The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell 10, 417–426 (2002).
5
P. S. Mitchell, A. Sandstrom, R. E. Vance, The NLRP1 inflammasome: New mechanistic insights and unresolved mysteries. Curr. Opin. Immunol. 60, 37–45 (2019).
6
A. Sandstrom, P. S. Mitchell, L. Goers, E. W. Mu, C. F. Lesser, R. E. Vance, Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes. Science 364, eaau1330 (2019).
7
A. J. Chui, M. C. Okondo, S. D. Rao, K. Gai, A. R. Griswold, D. C. Johnson, D. P. Ball, C. Y. Taabazuing, E. L. Orth, B. A. Vittimberga, D. A. Bachovchin, N-terminal degradation activates the NLRP1B inflammasome. Science 364, 82–85 (2019).
8
K. S. Robinson, D. E. T. Teo, K. S. Tan, G. A. Toh, H. H. Ong, C. K. Lim, K. Lay, B. V. Au, T. S. Lew, J. J. H. Chu, V. T. K. Chow, Y. Wang, F. L. Zhong, B. Reversade, Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science eaay2002 (2020).
9
M. C. Okondo, S. D. Rao, C. Y. Taabazuing, A. J. Chui, S. E. Poplawski, D. C. Johnson, D. A. Bachovchin, Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome. Cell Chem. Biol. 25, 262–267.e5 (2018).
10
D. C. Johnson, C. Y. Taabazuing, M. C. Okondo, A. J. Chui, S. D. Rao, F. C. Brown, C. Reed, E. Peguero, E. de Stanchina, A. Kentsis, D. A. Bachovchin, DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia. Nat. Med. 24, 1151–1156 (2018).
11
F. L. Zhong, K. Robinson, D. E. T. Teo, K.-Y. Tan, C. Lim, C. R. Harapas, C.-H. Yu, W. H. Xie, R. M. Sobota, V. B. Au, R. Hopkins, A. D’Osualdo, J. C. Reed, J. E. Connolly, S. L. Masters, B. Reversade, Human DPP9 represses NLRP1 inflammasome and protects against autoinflammatory diseases via both peptidase activity and FIIND domain binding. J. Biol. Chem. 293, 18864–18878 (2018).
12
S. B. Drutman, F. Haerynck, F. L. Zhong, D. Hum, N. J. Hernandez, S. Belkaya, F. Rapaport, S. J. de Jong, D. Creytens, S. J. Tavernier, K. Bonte, S. De Schepper, J. van der Werff Ten Bosch, L. Lorenzo-Diaz, A. Wullaert, X. Bossuyt, G. Orth, V. R. Bonagura, V. Béziat, L. Abel, E. Jouanguy, B. Reversade, J.-L. Casanova, Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis. Proc. Natl. Acad. Sci. U.S.A. 116, 19055–19063 (2019).
13
F. L. Zhong, O. Mamaï, L. Sborgi, L. Boussofara, R. Hopkins, K. Robinson, I. Szeverényi, T. Takeichi, R. Balaji, A. Lau, H. Tye, K. Roy, C. Bonnard, P. J. Ahl, L. A. Jones, P. J. Baker, L. Lacina, A. Otsuka, P. R. Fournie, F. Malecaze, E. B. Lane, M. Akiyama, K. Kabashima, J. E. Connolly, S. L. Masters, V. J. Soler, S. S. Omar, J. A. McGrath, R. Nedelcu, M. Gribaa, M. Denguezli, A. Saad, S. Hiller, B. Reversade, Germline NLRP1 mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation. Cell 167, 187–202.e17 (2016).
14
M. A. Dickson, W. C. Hahn, Y. Ino, V. Ronfard, J. Y. Wu, R. A. Weinberg, D. N. Louis, F. P. Li, J. G. Rheinwald, Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol. Cell. Biol. 20, 1436–1447 (2000).
15
S. Briolant, D. Garin, N. Scaramozzino, A. Jouan, J. M. Crance, In vitro inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: Synergistic effect of interferon-alpha and ribavirin combination. Antiviral Res. 61, 111–117 (2004).
16
M. Schlee, A. Roth, V. Hornung, C. A. Hagmann, V. Wimmenauer, W. Barchet, C. Coch, M. Janke, A. Mihailovic, G. Wardle, S. Juranek, H. Kato, T. Kawai, H. Poeck, K. A. Fitzgerald, O. Takeuchi, S. Akira, T. Tuschl, E. Latz, J. Ludwig, G. Hartmann, Recognition of 5′ triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity 31, 25–34 (2009).
17
L. Sun, J. Wu, F. Du, X. Chen, Z. J. Chen, Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).
18
T. D. Kanneganti, N. Ozören, M. Body-Malapel, A. Amer, J.-H. Park, L. Franchi, J. Whitfield, W. Barchet, M. Colonna, P. Vandenabeele, J. Bertin, A. Coyle, E. P. Grant, S. Akira, G. Núñez, Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3. Nature 440, 233–236 (2006).
19
J. Lilue, A. G. Doran, I. T. Fiddes, M. Abrudan, J. Armstrong, R. Bennett, W. Chow, J. Collins, S. Collins, A. Czechanski, P. Danecek, M. Diekhans, D.-D. Dolle, M. Dunn, R. Durbin, D. Earl, A. Ferguson-Smith, P. Flicek, J. Flint, A. Frankish, B. Fu, M. Gerstein, J. Gilbert, L. Goodstadt, J. Harrow, K. Howe, X. Ibarra-Soria, M. Kolmogorov, C. J. Lelliott, D. W. Logan, J. Loveland, C. E. Mathews, R. Mott, P. Muir, S. Nachtweide, F. C. P. Navarro, D. T. Odom, N. Park, S. Pelan, S. K. Pham, M. Quail, L. Reinholdt, L. Romoth, L. Shirley, C. Sisu, M. Sjoberg-Herrera, M. Stanke, C. Steward, M. Thomas, G. Threadgold, D. Thybert, J. Torrance, K. Wong, J. Wood, B. Yalcin, F. Yang, D. J. Adams, B. Paten, T. M. Keane, Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci. Nat. Genet. 50, 1574–1583 (2018).
20
K. Gai, M. C. Okondo, S. D. Rao, A. J. Chui, D. P. Ball, D. C. Johnson, D. A. Bachovchin, DPP8/9 inhibitors are universal activators of functional NLRP1 alleles. Cell Death Dis. 10, 587 (2019).
21
A. Peisley, C. Lin, B. Wu, M. Orme-Johnson, M. Liu, T. Walz, S. Hur, Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proc. Natl. Acad. Sci. U.S.A. 108, 21010–21015 (2011).
22
F. Civril, T. Deimling, C. C. de Oliveira Mann, A. Ablasser, M. Moldt, G. Witte, V. Hornung, K.-P. Hopfner, Structural mechanism of cytosolic DNA sensing by cGAS. Nature 498, 332–337 (2013).
23
J. A. Duncan, D. T. Bergstralh, Y. Wang, S. B. Willingham, Z. Ye, A. G. Zimmermann, J. P.-Y. Ting, Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc. Natl. Acad. Sci. U.S.A. 104, 8041–8046 (2007).
24
R. C. Coll, J. R. Hill, C. J. Day, A. Zamoshnikova, D. Boucher, N. L. Massey, J. L. Chitty, J. A. Fraser, M. P. Jennings, A. A. B. Robertson, K. Schroder, MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat. Chem. Biol. 15, 556–559 (2019).
25
Z. Hu, C. Yan, P. Liu, Z. Huang, R. Ma, C. Zhang, R. Wang, Y. Zhang, F. Martinon, D. Miao, H. Deng, J. Wang, J. Chang, J. Chai, Crystal structure of NLRC4 reveals its autoinhibition mechanism. Science 341, 172–175 (2013).
26
P. A. Harris, C. Duraiswami, D. T. Fisher, J. Fornwald, S. J. Hoffman, G. Hofmann, M. Jiang, R. Lehr, P. M. McCormick, L. Nickels, B. Schwartz, Z. Wu, G. Zhang, R. W. Marquis, J. Bertin, P. J. Gough, High throughput screening identifies ATP-competitive inhibitors of the NLRP1 inflammasome. Bioorg. Med. Chem. Lett. 25, 2739–2743 (2015).
27
J. Chavarría-Smith, P. S. Mitchell, A. M. Ho, M. D. Daugherty, R. E. Vance, Functional and evolutionary analyses identify proteolysis as a general mechanism for NLRP1 inflammasome activation. PLOS Pathog. 12, e1006052 (2016).
28
R. D. George, G. McVicker, R. Diederich, S. B. Ng, A. P. MacKenzie, W. J. Swanson, J. Shendure, J. H. Thomas, Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection. Genome Res. 21, 1686–1694 (2011).
29
B. Wu, A. Peisley, C. Richards, H. Yao, X. Zeng, C. Lin, F. Chu, T. Walz, S. Hur, Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell 152, 276–289 (2013).
30
M. M. Gaidt, T. S. Ebert, D. Chauhan, K. Ramshorn, F. Pinci, S. Zuber, F. O’Duill, J. L. Schmid-Burgk, F. Hoss, R. Buhmann, G. Wittmann, E. Latz, M. Subklewe, V. Hornung, The DNA Inflammasome in human myeloid cells is initiated by a STING-cell death program upstream of NLRP3. Cell 171, 1110–1124.e18 (2017).
31
A. Linder, S. Bauernfried, Y. Cheng, M. Albanese, C. Jung, O. T. Keppler, V. Hornung, CARD8 inflammasome activation triggers pyroptosis in human T cells. EMBO J. 39, e105071 (2020).
32
A. Stutz, G. L. Horvath, B. G. Monks, E. Latz, ASC speck formation as a readout for inflammasome activation. Methods Mol. Biol. 1040, 91–101 (2013).
33
C. Jakobs, E. Bartok, A. Kubarenko, F. Bauernfeind, V. Hornung, Immunoblotting for active caspase-1. Methods Mol. Biol. 1040, 103–115 (2013).
34
F. Hoss, V. Rolfes, M. R. Davanso, T. T. Braga, B. S. Franklin, Detection of ASC speck formation by flow cytometry and chemical cross-linking. Methods Mol. Biol. 1714, 149–165 (2018).
35
B. He, M. Rong, D. Lyakhov, H. Gartenstein, G. Diaz, R. Castagna, W. T. McAllister, R. K. Durbin, Rapid mutagenesis and purification of phage RNA polymerases. Protein Expr. Purif. 9, 142–151 (1997).
36
J. Moecking, “Investigating the molecular basis of human NLRP1 inflammasome activation,” thesis, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Melbourne (2020).
37
I. Rubio, R. Pusch, R. Wetzker, Quantification of absolute Ras-GDP/GTP levels by HPLC separation of Ras-bound [(32)P]-labelled nucleotides. J. Biochem. Biophys. Methods 58, 111–117 (2004).
38
D. C. Rawling, M. E. Fitzgerald, A. M. Pyle, Establishing the role of ATP for the function of the RIG-I innate immune sensor. eLife 4, e09391 (2015).
39
L. Zimmermann, A. Stephens, S.-Z. Nam, D. Rau, J. Kübler, M. Lozajic, F. Gabler, J. Söding, A. N. Lupas, V. Alva, A completely reimplemented MPI bioinformatics toolkit with a new HHpred server at its core. J. Mol. Biol. 430, 2237–2243 (2018).

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Science
Volume 371 | Issue 6528
29 January 2021

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Received: 4 June 2020
Accepted: 18 November 2020
Published in print: 29 January 2021

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Acknowledgments

We kindly thank L. Hansbauer and A. Wegerer (Gene Center, LMU) for great technical support; J. Rech (Gene Center, LMU) for help with robotic support; A. Linder (Gene Center, LMU) for CARD8/− THP1; R. Vance (UC Berkeley, USA) for providing us with the NeedleTox expression plasmid; M. Moldt and K.-P. Hopfner (Gene Center, LMU) for help producing the NeedleTox protein; C. Stafford (Gene Center, LMU) for purification of the NeedleTox protein; S. Suppmann and J. Scholz (MPI, Munich) for expressing recombinant NLRP1 in insect cells as well as providing us with recombinant MBP, EGF, and MCSF; S. Uebel (MPI, Munich) for ATP/ADP HPLC sample preparation and measurement; C. Basquin (MPI, Munich) for advice with fluorescence anisotropy measurements; J. Rheinwald (Harvard University, USA) for the N/TERT-1 cell line; E. van den Bogaard and J. P. Smits (Radboud University Nijmegen, Netherlands) for providing us with N/TERT-1; R. Buhman and A. Humpe (Department of Transfusion Medicine, LMU) for providing leukocyte reduction system chambers; G. Sutter and J. Rojas (Faculty of Veterinary Medicine, LMU) for providing us with MVA, V. Girault (Institute of Virology, TUM) for help with HSV-1 infections; and A. Hennrich and Klaus Conzelmann (Gene Center, LMU) for providing us with MV. Virus depictions in Fig. 1 were generated using BioRender. Funding: This work was supported by the European Research Council (grant no. ERC-2014-CoG–647858 GENESIS to V.H. and grant no. ERC-2018-CoG–817798 ProDAP to A.P.), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation grant no. TRR 237/A09, project ID 369799452, to V.H. and grant no. DFG TRR 237/A07 to A.P., CRC grant no. 1335/P015, project ID 360372040, and grant no. SPP 1923, project ID 273898015, to V.H., and grant no. TRR 179/TP11, project ID 272983813, to A.P). K.E.D. is funded by a starting grant from the ERC (grant no. ERC-2018-StG–804098 REPLISOMEBYPASS) and by the Max Planck Society. Author contributions: Conceptualization, S.B. and V.H.; Funding acquisition, V.H.; Investigation, S.B. and M.S.; Resources, A.P., K.D., and V.H.; Supervision, V.H.; Writing, V.H. with input from all authors. Competing interests: V.H. serves on the Scientific Advisory Board of Inflazome Ltd. The remaining authors declare no competing interests. Data and materials availability: All data are available in the main text or the supplementary materials

Authors

Affiliations

Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Max-Planck Institute of Biochemistry, Martinsried, Germany.
Institute of Virology, Technical University of Munich, School of Medicine, Munich, Germany.
German Center for Infection Research (DZIF), Munich, Germany.
Max-Planck Institute of Biochemistry, Martinsried, Germany.
Physics Department, Technical University of Munich, Garching, Germany.
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
Max-Planck Institute of Biochemistry, Martinsried, Germany.

Funding Information

European Research Council: ERC-2014-CoG – 647858 GENESIS
European Research Council: ERC-2018-CoG – 817798 ProDAP
European Research Council: ERC-2018-StG – 804098 REPLISOMEBYPASS
Deutsche Forschungsgemeinschaft: TRR 237/A09 (Project-ID 369799452)
Deutsche Forschungsgemeinschaft: CRC 1335/P015 (Project-ID 360372040)
Deutsche Forschungsgemeinschaft: SPP 1923 (Project-ID 273898015)
Deutsche Forschungsgemeinschaft: TRR 179/TP11 (Project-ID 272983813)
Deutsche Forschungsgemeinschaft: TRR 237/A07 (Project-ID 369799452)

Notes

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Corresponding author. Email: [email protected]

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