NAD prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages.
Authors:
Journal: eLife
Publication Type: Journal Article
Date: 2024
DOI: PMC10942599
ID: 38372712
Abstract
Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and proinflammatory cytokine production via caspase-11 and gasdermin D (GSDMD). Here, we show that NAD treatment protected mice toward bacterial and lipopolysaccharide (LPS)-induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD administration impeded systemic IL-1β and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-β/STAT-1 signaling machinery. More importantly, NAD administration not only improved casp-11 KO (knockout) survival but rendered wild type (WT) mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.
Chemical List
- Cytokines|||Interleukin-10|||Inflammasomes|||NAD
Reference List
- Angus DC, van der Poll T. Severe sepsis and septic shock. The New England Journal of Medicine. 2013;369:840–851. doi: 10.1056/NEJMra1208623.|||Apelbaum A, Yarden G, Warszawski S, Harari D, Schreiber G. Type I interferons induce apoptosis by balancing cFLIP and caspase-8 independent of death ligands. Molecular and Cellular Biology. 2013;33:800–814. doi: 10.1128/MCB.01430-12.|||Begue B, Verdier J, Rieux-Laucat F, Goulet O, Morali A, Canioni D, Hugot J-P, Daussy C, Verkarre V, Pigneur B, Fischer A, Klein C, Cerf-Bensussan N, Ruemmele FM. Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease. The American Journal of Gastroenterology. 2011;106:1544–1555. doi: 10.1038/ajg.2011.112.|||Berg DJ, Kühn R, Rajewsky K, Müller W, Menon S, Davidson N, Grünig G, Rennick D. Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance. The Journal of Clinical Investigation. 1995;96:2339–2347. doi: 10.1172/JCI118290.|||Bullock B, Benham MD. In: StatPearls. Bullock B, editor. StatPearls Publishing StatPearls Publishing LLC; 2019. Bacterial sepsis.|||Chan FK-M, Moriwaki K, De Rosa MJ. Detection of necrosis by release of lactate dehydrogenase activity. Methods in Molecular Biology. 2013;979:65–70. doi: 10.1007/978-1-62703-290-2_7.|||de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. The Journal of Experimental Medicine. 1991;174:1209–1220. doi: 10.1084/jem.174.5.1209.|||Ding J, Shao F. Snapshot: The noncanonical inflammasome. Cell. 2017;168:544. doi: 10.1016/j.cell.2017.01.008.|||Dogan MD, Ataoglu H, Akarsu ES. Effects of different serotypes of Escherichia coli lipopolysaccharides on body temperature in rats. Life Sciences. 2000;67:2319–2329. doi: 10.1016/s0024-3205(00)00821-3.|||Elkhal A, Rodriguez Cetina Biefer H, Heinbokel T, Uehara H, Quante M, Seyda M, Schuitenmaker JM, Krenzien F, Camacho V, de la Fuente MA, Ghiran I, Tullius SG. NAD(+) regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4(+) CD25(+) Foxp3(+) T cells independent. Scientific Reports. 2016;6:22325. doi: 10.1038/srep22325.|||Evans TJ. The role of macrophages in septic shock. Immunobiology. 1996;195:655–659. doi: 10.1016/S0171-2985(96)80029-5.|||Farber JM, Peterkin PI. Listeria monocytogenes, a food-borne pathogen. Microbiological Reviews. 1991;55:476–511. doi: 10.1128/mr.55.3.476-511.1991.|||Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. Journal of Immunology. 1991;147:3815–3822.|||Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G, Domingues FS, Albrecht M, Nothnagel M, Ellinghaus D, Sina C, Onnie CM, Weersma RK, Stokkers PCF, Wijmenga C, Gazouli M, Strachan D, McArdle WL, Vermeire S, Rutgeerts P, Rosenstiel P, Krawczak M, Vatn MH, IBSEN study group. Mathew CG, Schreiber S. Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nature Genetics. 2008;40:1319–1323. doi: 10.1038/ng.221.|||Franke A, McGovern DPB, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Cohen A, Colombel J-F, Cottone M, Stronati L, Denson T, De Vos M, D’Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, Van Gossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot J-P, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panés J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PCF, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D’Amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, Parkes M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nature Genetics. 2010;42:1118–1125. doi: 10.1038/ng.717.|||Fraser CC. Exploring the Positive and Negative Consequences of NF-κB Inhibition for the Treatment of Human Disease. Cell Cycle. 2006;5:1160–1163. doi: 10.4161/cc.5.11.2773.|||Greenhill CJ, Jones GW, Nowell MA, Newton Z, Harvey AK, Moideen AN, Collins FL, Bloom AC, Coll RC, Robertson AAB, Cooper MA, Rosas M, Taylor PR, O’Neill LA, Humphreys IR, Williams AS, Jones SA. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Research & Therapy. 2014;16:419. doi: 10.1186/s13075-014-0419-y.|||Hagar JA, Edin ML, Lih FB, Thurlow LR, Koller BH, Cairns BA, Zeldin DC, Miao EA. Lipopolysaccharide Potentiates Insulin-Driven Hypoglycemic Shock. Journal of Immunology. 2017;199:3634–3643. doi: 10.4049/jimmunol.1700820.|||Howard M, Muchamuel T, Andrade S, Menon S. Interleukin 10 protects mice from lethal endotoxemia. The Journal of Experimental Medicine. 1993;177:1205–1208. doi: 10.1084/jem.177.4.1205.|||Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nature Reviews. Immunology. 2014;14:36–49. doi: 10.1038/nri3581.|||Kaukonen KM, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Systemic inflammatory response syndrome criteria in defining severe sepsis. The New England Journal of Medicine. 2015;372:1629–1638. doi: 10.1056/NEJMoa1415236.|||Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479:117–121. doi: 10.1038/nature10558.|||Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, Miyake K, Zhang J, Lee WP, Muszyński A, Forsberg LS, Carlson RW, Dixit VM. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science. 2013;341:1246–1249. doi: 10.1126/science.1240248.|||Kayagaki N, Stowe IB, Lee BL, O’Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015;526:666–671. doi: 10.1038/nature15541.|||Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75:263–274. doi: 10.1016/0092-8674(93)80068-p.|||Kumar V. Inflammasomes: Pandora’s box for sepsis. Journal of Inflammation Research. 2018;11:477–502. doi: 10.2147/JIR.S178084.|||Latifi SQ, O’Riordan MA, Levine AD. Interleukin-10 controls the onset of irreversible septic shock. Infection and Immunity. 2002;70:4441–4446. doi: 10.1128/IAI.70.8.4441-4446.2002.|||Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy. 2017;2:17023. doi: 10.1038/sigtrans.2017.23.|||Lopez-Castejon G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine & Growth Factor Reviews. 2011;22:189–195. doi: 10.1016/j.cytogfr.2011.10.001.|||Man SM, Karki R, Briard B, Burton A, Gingras S, Pelletier S, Kanneganti T-D. Differential roles of caspase-1 and caspase-11 in infection and inflammation. Scientific Reports. 2017;7:45126. doi: 10.1038/srep45126.|||Mandal P, Feng Y, Lyons JD, Berger SB, Otani S, DeLaney A, Tharp GK, Maner-Smith K, Burd EM, Schaeffer M, Hoffman S, Capriotti C, Roback L, Young CB, Liang Z, Ortlund EA, DiPaolo NC, Bosinger S, Bertin J, Gough PJ, Brodsky IE, Coopersmith CM, Shayakhmetov DM, Mocarski ES. Caspase-8 Collaborates with Caspase-11 to Drive Tissue Damage and Execution of Endotoxic Shock. Immunity. 2018;49:42–55. doi: 10.1016/j.immuni.2018.06.011.|||Mellata M, Mitchell NM, Schödel F, Curtiss R, Pier GB. Novel vaccine antigen combinations elicit protective immune responses against Escherichia coli sepsis. Vaccine. 2016;34:656–662. doi: 10.1016/j.vaccine.2015.12.014.|||Newton K, Wickliffe KE, Dugger DL, Maltzman A, Roose-Girma M, Dohse M, Kőműves L, Webster JD, Dixit VM. Cleavage of RIPK1 by caspase-8 is crucial for limiting apoptosis and necroptosis. Nature. 2019;574:428–431. doi: 10.1038/s41586-019-1548-x.|||Pilla DM, Hagar JA, Haldar AK, Mason AK, Degrandi D, Pfeffer K, Ernst RK, Yamamoto M, Miao EA, Coers J. Guanylate binding proteins promote caspase-11-dependent pyroptosis in response to cytoplasmic LPS. PNAS. 2014;111:6046–6051. doi: 10.1073/pnas.1321700111.|||Ramachandran G. Gram-positive and gram-negative bacterial toxins in sepsis: a brief review. Virulence. 2014;5:213–218. doi: 10.4161/viru.27024.|||Rathinam VAK, Vanaja SK, Waggoner L, Sokolovska A, Becker C, Stuart LM, Leong JM, Fitzgerald KA. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria. Cell. 2012;150:606–619. doi: 10.1016/j.cell.2012.07.007.|||Rodriguez Cetina Biefer H, Heinbokel T, Uehara H, Camacho V, Minami K, Nian Y, Koduru S, El Fatimy R, Ghiran I, Trachtenberg AJ, de la Fuente MA, Azuma H, Akbari O, Tullius SG, Vasudevan A, Elkhal A. Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation. The Journal of Allergy and Clinical Immunology. 2018;142:1894–1908. doi: 10.1016/j.jaci.2018.01.038.|||Rossaint J, Zarbock A. Pathogenesis of multiple organ failure in sepsis. Critical Reviews in Immunology. 2015;35:277–291. doi: 10.1615/critrevimmunol.2015015461.|||Schauvliege R, Vanrobaeys J, Schotte P, Beyaert R. Caspase-11 gene expression in response to lipopolysaccharide and interferon-gamma requires nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 1. The Journal of Biological Chemistry. 2002;277:41624–41630. doi: 10.1074/jbc.M207852200.|||Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annual Review of Immunology. 2014;32:513–545. doi: 10.1146/annurev-immunol-032713-120231.|||Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014;514:187–192. doi: 10.1038/nature13683.|||Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660–665. doi: 10.1038/nature15514.|||Stark GR, Darnell JE. The JAK-STAT pathway at twenty. Immunity. 2012;36:503–514. doi: 10.1016/j.immuni.2012.03.013.|||Sun Y, Ma J, Li D, Li P, Zhou X, Li Y, He Z, Qin L, Liang L, Luo X. Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures. Journal of Neuroinflammation. 2019;16:66. doi: 10.1186/s12974-019-1452-1.|||Tang Y, Zhang R, Xue Q, Meng R, Wang X, Yang Y, Xie L, Xiao X, Billiar TR, Lu B. TRIF signaling is required for caspase-11-dependent immune responses and lethality in sepsis. Molecular Medicine. 2018;24:66. doi: 10.1186/s10020-018-0065-y.|||Tullius SG, Biefer HRC, Li S, Trachtenberg AJ, Edtinger K, Quante M, Krenzien F, Uehara H, Yang X, Kissick HT, Kuo WP, Ghiran I, de la Fuente MA, Arredouani MS, Camacho V, Tigges JC, Toxavidis V, El Fatimy R, Smith BD, Vasudevan A, ElKhal A. NAD+ protects against EAE by regulating CD4+ T-cell differentiation. Nature Communications. 2014;5:5101. doi: 10.1038/ncomms6101.|||Yang D, He Y, Muñoz-Planillo R, Liu Q, Núñez G. Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock. Immunity. 2015a;43:923–932. doi: 10.1016/j.immuni.2015.10.009.|||Yang J, Zhao Y, Shao F. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Current Opinion in Immunology. 2015b;32:78–83. doi: 10.1016/j.coi.2015.01.007.|||Yao Y, Vent-Schmidt J, McGeough MD, Wong M, Hoffman HM, Steiner TS, Levings MK. Tr1 Cells, but Not Foxp3+ Regulatory T Cells, Suppress NLRP3 Inflammasome Activation via an IL-10-Dependent Mechanism. Journal of Immunology. 2015;195:488–497. doi: 10.4049/jimmunol.1403225.|||Yen JH, Ganea D. Interferon beta induces mature dendritic cell apoptosis through caspase-11/caspase-3 activation. Blood. 2009;114:1344–1354. doi: 10.1182/blood-2008-12-196592.|||Yi YS. Caspase-11 non-canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage-mediated inflammatory responses. Immunology. 2017;152:207–217. doi: 10.1111/imm.12787.|||Zhang J, Fu S, Sun S, Li Z, Guo B. Inflammasome activation has an important role in the development of spontaneous colitis. Mucosal Immunology. 2014;7:1139–1150. doi: 10.1038/mi.2014.1.