Taking AIM at Influenza: The Role of the AIM2 Inflammasome
Abstract
1. Introduction
Innate Immune Response to Infection
2. AIM2 Inflammasome in Response to Viral Infections
2.1. DNA Viruses
2.2. RNA Viruses
3. AIM2 Inflammasome Is Activated during IAV Infection
Methodological Aspect | Studies/Year | ||
---|---|---|---|
Schattgen et al. (2016) [37] | Zhang et al. (2017) [36] | Moriyama et al. (2020) [66] | |
Key influenza infection findings | Transient reduction of IL-1β, IL-6, and TNF secretion in lung homogenates from Aim2−/− mice at 3 dpi. Increased albumin in BALF 3 dpi, and CD4+, CD8+ T cells, and immature macrophages in the lung of Aim2−/− mice at 5 dpi. Aim2−/− mice displayed reduced survival. | siRNA knockout of AIM2 reduced IL-1β, TNF, and CCL5 secretion from primary human macrophages but not epithelial cells. Reduced pro- and cleaved-forms of caspase-1 and IL-1β in lung tissue and BALF 3 dpi of Aim2−/− mice. Reduced LDH, albumin, TNF, and infiltration of inflammatory cells in the lung of Aim2−/− mice at 3 dpi. Aim2−/− mice displayed improved survival and reduced lung damage 9 dpi. | Reduced IL-1β secretion in Aim2−/− BMDMs. |
Study model | C57BL/6 mice | Human alveolar macrophages and alveolar epithelial type II cells C57BL/6J mice | Murine primary BMDMs |
Animal source | Aim2−/− mice generated in-house and backcrossed to C57BL/6 mice. | Aim2−/− mice (The Jackson Laboratory) backcrossed to C57BL/6J (The Jackson Laboratory) | N/A |
Virus Strain | A/Puerto Rico/8/34 H1N1 | A/Puerto Rico/8/34 H1N1 A/California/07/09 H1N1 | A/Puerto Rico/8/34 H1N1 |
Virus Preparation | Embryonated chicken eggs | Madin-Darby Canine Kidney cells | Embryonated chicken eggs |
Viral Dose | Mice: 40,000 PFU in 30 µL PBS | Cells: MOI of 1 Mice: 40/4000 PFU (A/PR/8/34) or 5000/500,000 PFU (A/CA/07/09) in 50 µL DMEM | Cells: MOI of 3–10 |
In vivo route of infection | Intranasal | Intranasal and intratracheal | N/A |
4. Possible Molecular Pathways Mediating AIM2 Activation in IAV
4.1. Exogenous DNA
4.2. Cross-Talk between DNA and RNA Sensors
4.3. Viral Proteins
5. Therapeutic Potential of AIM2 in Influenza
5.1. Targeting Components of the AIM2 Inflammasome
5.2. Targeting Release of Self-DNA
5.3. Targeting Caspase-1
6. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- WHO. Influenza (Seasonal)—Fact Sheet. Available online: https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) (accessed on 24 September 2024).
- Yoon, S.-W.; Webby, R.J.; Webster, R.G. Evolution and Ecology of Influenza A Viruses. In Influenza Pathogenesis and Control—Volume I; Compans, R.W., Oldstone, M.B.A., Eds.; Springer International Publishing: Cham, Switzerland, 2014; pp. 359–375. [Google Scholar] [CrossRef]
- Kim, H.; Webster, R.G.; Webby, R.J. Influenza Virus: Dealing with a Drifting and Shifting Pathogen. Viral Immunol. 2018, 31, 174–183. [Google Scholar] [CrossRef] [PubMed]
- Webster, R.G.; Laver, W.G.; Air, G.M.; Schild, G.C. Molecular mechanisms of variation in influenza viruses. Nature 1982, 296, 115–121. [Google Scholar] [CrossRef]
- Ryu, W.-S. Chapter 15—Influenza Viruses. In Molecular Virology of Human Pathogenic Viruses; Ryu, W.-S., Ed.; Academic Press: Boston, MA, USA, 2017; pp. 195–211. [Google Scholar] [CrossRef]
- Johnson, N.P.; Mueller, J. Updating the accounts: Global mortality of the 1918-1920 “Spanish” influenza pandemic. Bull. Hist. Med. 2002, 76, 105–115. [Google Scholar] [CrossRef]
- WHO. 2009 H1N1 Pandemic (H1N1 pdm09 Virus). Available online: https://archive.cdc.gov/www_cdc_gov/flu/pandemic-resources/2009-h1n1-pandemic.html#:~:text=Additionally%2C%20CDC%20estimated%20that%20151%2C700,than%2065%20years%20of%20age (accessed on 24 September 2024).
- Laghlali, G.; Lawlor, K.E.; Tate, M.D. Die Another Way: Interplay between Influenza A Virus, Inflammation and Cell Death. Viruses 2020, 12, 401. [Google Scholar] [CrossRef] [PubMed]
- Liu, Q.; Zhou, Y.-h.; Yang, Z.-q. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell. Mol. Immunol. 2016, 13, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Guo, X.J.; Thomas, P.G. New fronts emerge in the influenza cytokine storm. Semin. Immunopathol. 2017, 39, 541–550. [Google Scholar] [CrossRef] [PubMed]
- Short, K.R.; Kroeze, E.J.B.V.; Fouchier, R.A.M.; Kuiken, T. Pathogenesis of influenza-induced acute respiratory distress syndrome. Lancet Infect. Dis. 2014, 14, 57–69. [Google Scholar] [CrossRef]
- Herold, S.; Becker, C.; Ridge, K.M.; Budinger, G.R.S. Influenza virus-induced lung injury: Pathogenesis and implications for treatment. Eur. Respir. J. 2015, 45, 1463. [Google Scholar] [CrossRef]
- Gu, Y.; Hsu, A.C.-Y.; Pang, Z.; Pan, H.; Zuo, X.; Wang, G.; Zheng, J.; Wang, F. Role of the Innate Cytokine Storm Induced by the Influenza A Virus. Viral Immunol. 2019, 32, 244–251. [Google Scholar] [CrossRef]
- Batool, S.; Chokkakula, S.; Song, M.S. Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy. Microorganisms 2023, 11, 183. [Google Scholar] [CrossRef]
- Takeuchi, O.; Akira, S. Pattern Recognition Receptors and Inflammation. Cell 2010, 140, 805–820. [Google Scholar] [CrossRef] [PubMed]
- Lund, J.M.; Alexopoulou, L.; Sato, A.; Karow, M.; Adams, N.C.; Gale, N.W.; Iwasaki, A.; Flavell, R.A. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 2004, 101, 5598–5603. [Google Scholar] [CrossRef] [PubMed]
- Guillot, L.; Le Goffic, R.; Bloch, S.; Escriou, N.; Akira, S.; Chignard, M.; Si-Tahar, M. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J. Biol. Chem. 2005, 280, 5571–5580. [Google Scholar] [CrossRef] [PubMed]
- Kato, H.; Takeuchi, O.; Sato, S.; Yoneyama, M.; Yamamoto, M.; Matsui, K.; Uematsu, S.; Jung, A.; Kawai, T.; Ishii, K.J.; et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006, 441, 101–105. [Google Scholar] [CrossRef]
- Le Goffic, R.; Pothlichet, J.; Vitour, D.; Fujita, T.; Meurs, E.; Chignard, M.; Si-Tahar, M. Cutting Edge: Influenza A Virus Activates TLR3-Dependent Inflammatory and RIG-I-Dependent Antiviral Responses in Human Lung Epithelial Cells1. J. Immunol. 2007, 178, 3368–3372. [Google Scholar] [CrossRef]
- Allen, I.C.; Scull, M.A.; Moore, C.B.; Holl, E.K.; McElvania-TeKippe, E.; Taxman, D.J.; Guthrie, E.H.; Pickles, R.J.; Ting, J.P.Y. The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA. Immunity 2009, 30, 556–565. [Google Scholar] [CrossRef]
- Ichinohe, T.; Pang, I.K.; Iwasaki, A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat. Immunol. 2010, 11, 404–410. [Google Scholar] [CrossRef]
- Pandey, K.P.; Zhou, Y. Influenza A Virus Infection Activates NLRP3 Inflammasome through Trans-Golgi Network Dispersion. Viruses 2022, 14, 88. [Google Scholar] [CrossRef] [PubMed]
- McAuley, J.L.; Tate, M.D.; MacKenzie-Kludas, C.J.; Pinar, A.; Zeng, W.; Stutz, A.; Latz, E.; Brown, L.E.; Mansell, A. Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog. 2013, 9, e1003392. [Google Scholar] [CrossRef]
- Latz, E.; Xiao, T.S.; Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 2013, 13, 397–411. [Google Scholar] [CrossRef]
- Pinar, A.; Dowling, J.K.; Bitto, N.J.; Robertson, A.A.; Latz, E.; Stewart, C.R.; Drummond, G.R.; Cooper, M.A.; McAuley, J.L.; Tate, M.D.; et al. PB1-F2 Peptide Derived from Avian Influenza A Virus H7N9 Induces Inflammation via Activation of the NLRP3 Inflammasome. J. Biol. Chem. 2017, 292, 826–836. [Google Scholar] [CrossRef] [PubMed]
- Sharma, D.; Kanneganti, T.D. The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation. J. Cell Biol. 2016, 213, 617–629. [Google Scholar] [CrossRef] [PubMed]
- Martinon, F.; Burns, K.; Tschopp, J. The Inflammasome: A Molecular Platform Triggering Activation of Inflammatory Caspases and Processing of proIL-β. Mol. Cell 2002, 10, 417–426. [Google Scholar] [CrossRef] [PubMed]
- Tate, M.D.; Ong, J.D.H.; Dowling, J.K.; McAuley, J.L.; Robertson, A.B.; Latz, E.; Drummond, G.R.; Cooper, M.A.; Hertzog, P.J.; Mansell, A. Reassessing the role of the NLRP3 inflammasome during pathogenic influenza A virus infection via temporal inhibition. Sci. Rep. 2016, 6, 27912. [Google Scholar] [CrossRef]
- Ren, R.; Wu, S.; Cai, J.; Yang, Y.; Ren, X.; Feng, Y.; Chen, L.; Qin, B.; Xu, C.; Yang, H.; et al. The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome. Sci. Rep. 2017, 7, 7625. [Google Scholar] [CrossRef]
- Docherty, C.A.; Fernando, A.J.; Rosli, S.; Lam, M.; Dolle, R.E.; Navia, M.A.; Farquhar, R.; La France, D.; Tate, M.D.; Murphy, C.K.; et al. A novel dual NLRP1 and NLRP3 inflammasome inhibitor for the treatment of inflammatory diseases. Clin. Transl. Immunol. 2023, 12, e1455. [Google Scholar] [CrossRef]
- Bawazeer, A.O.; Rosli, S.; Harpur, C.M.; Docherty, C.A.; Mansell, A.; Tate, M.D. Interleukin-1β exacerbates disease and is a potential therapeutic target to reduce pulmonary inflammation during severe influenza A virus infection. Immunol. Cell Biol. 2021, 99, 737–748. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- He, W.T.; Wan, H.; Hu, L.; Chen, P.; Wang, X.; Huang, Z.; Yang, Z.H.; Zhong, C.Q.; Han, J. Gasdermin D is an executor of pyroptosis and required for interleukin-1β secretion. Cell Res. 2015, 25, 1285–1298. [Google Scholar] [CrossRef]
- Kayagaki, N.; Stowe, I.B.; Lee, B.L.; O’Rourke, K.; Anderson, K.; Warming, S.; Cuellar, T.; Haley, B.; Roose-Girma, M.; Phung, Q.T.; et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 2015, 526, 666–671. [Google Scholar] [CrossRef]
- Rosli, S.; Harpur, C.M.; Lam, M.; West, A.C.; Hodges, C.; Mansell, A.; Lawlor, K.E.; Tate, M.D. Gasdermin D promotes hyperinflammation and immunopathology during severe influenza A virus infection. Cell Death Dis. 2023, 14, 727. [Google Scholar] [CrossRef] [PubMed]
- Zhang, H.; Luo, J.; Alcorn, J.F.; Chen, K.; Fan, S.; Pilewski, J.; Liu, A.; Chen, W.; Kolls, J.K.; Wang, J. AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality. J. Immunol. 2017, 198, 4383–4393. [Google Scholar] [CrossRef] [PubMed]
- Schattgen, S.A.; Gao, G.; Kurt-Jones, E.A.; Fitzgerald, K.A. Cutting Edge: DNA in the Lung Microenvironment during Influenza Virus Infection Tempers Inflammation by Engaging the DNA Sensor AIM2. J. Immunol. 2016, 196, 29–33. [Google Scholar] [CrossRef]
- Bürckstümmer, T.; Baumann, C.; Blüml, S.; Dixit, E.; Dürnberger, G.; Jahn, H.; Planyavsky, M.; Bilban, M.; Colinge, J.; Bennett, K.L.; et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 2009, 10, 266–272. [Google Scholar] [CrossRef]
- Colarusso, C.; Terlizzi, M.; Maglio, A.; Molino, A.; Candia, C.; Vitale, C.; Hansbro, P.M.; Vatrella, A.; Pinto, A.; Sorrentino, R. Activation of the AIM2 Receptor in Circulating Cells of Post-COVID-19 Patients With Signs of Lung Fibrosis Is Associated With the Release of IL-1α, IFN-α and TGF-β. Front. Immunol. 2022, 13, 934264. [Google Scholar] [CrossRef]
- Junqueira, C.; Crespo, Â.; Ranjbar, S.; de Lacerda, L.B.; Lewandrowski, M.; Ingber, J.; Parry, B.; Ravid, S.; Clark, S.; Schrimpf, M.R.; et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature 2022, 606, 576–584. [Google Scholar] [CrossRef]
- Andargie, T.E.; Tsuji, N.; Seifuddin, F.; Jang, M.K.; Yuen, P.S.; Kong, H.; Tunc, I.; Singh, K.; Charya, A.; Wilkins, K.; et al. Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. JCI Insight 2021, 6, e147610. [Google Scholar] [CrossRef]
- Kaivola, J.; Nyman, T.A.; Matikainen, S. Inflammasomes and SARS-CoV-2 Infection. Viruses 2021, 13, 2513. [Google Scholar] [CrossRef] [PubMed]
- Cerato, J.A.; da Silva, E.F.; Porto, B.N. Breaking Bad: Inflammasome Activation by Respiratory Viruses. Biology 2023, 12, 943. [Google Scholar] [CrossRef]
- 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 2009, 458, 509–513. [Google Scholar] [CrossRef]
- Hornung, V.; Ablasser, A.; Charrel-Dennis, M.; Bauernfeind, F.; Horvath, G.; Caffrey, D.R.; Latz, E.; Fitzgerald, K.A. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2009, 458, 514–518. [Google Scholar] [CrossRef] [PubMed]
- Roberts, T.L.; Idris, A.; Dunn, J.A.; Kelly, G.M.; Burnton, C.M.; Hodgson, S.; Hardy, L.L.; Garceau, V.; Sweet, M.J.; Ross, I.L.; et al. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science 2009, 323, 1057–1060. [Google Scholar] [CrossRef] [PubMed]
- Jin, T.; Perry, A.; Smith, P.; Jiang, J.; Xiao, T.S. Structure of the absent in melanoma 2 (AIM2) pyrin domain provides insights into the mechanisms of AIM2 autoinhibition and inflammasome assembly. J. Biol. Chem. 2013, 288, 13225–13235. [Google Scholar] [CrossRef] [PubMed]
- Muruve, D.A.; Pétrilli, V.; Zaiss, A.K.; White, L.R.; Clark, S.A.; Ross, P.J.; Parks, R.J.; Tschopp, J. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 2008, 452, 103–107. [Google Scholar] [CrossRef] [PubMed]
- Rathinam, V.A.K.; Jiang, Z.; Waggoner, S.N.; Sharma, S.; Cole, L.E.; Waggoner, L.; Vanaja, S.K.; Monks, B.G.; Ganesan, S.; Latz, E.; et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 2010, 11, 395–402. [Google Scholar] [CrossRef]
- Reinholz, M.; Kawakami, Y.; Salzer, S.; Kreuter, A.; Dombrowski, Y.; Koglin, S.; Kresse, S.; Ruzicka, T.; Schauber, J. HPV16 activates the AIM2 inflammasome in keratinocytes. Arch. Dermatol. Res. 2013, 305, 723–732. [Google Scholar] [CrossRef]
- Torii, Y.; Kawada, J.-i.; Murata, T.; Yoshiyama, H.; Kimura, H.; Ito, Y. Epstein-Barr virus infection-induced inflammasome activation in human monocytes. PLoS ONE 2017, 12, e0175053. [Google Scholar] [CrossRef]
- Maruzuru, Y.; Koyanagi, N.; Kato, A.; Kawaguchi, Y. Role of the DNA Binding Activity of Herpes Simplex Virus 1 VP22 in Evading AIM2-Dependent Inflammasome Activation Induced by the Virus. J. Virol. 2021, 95, e02172-20. [Google Scholar] [CrossRef]
- Maruzuru, Y.; Ichinohe, T.; Sato, R.; Miyake, K.; Okano, T.; Suzuki, T.; Koshiba, T.; Koyanagi, N.; Tsuda, S.; Watanabe, M.; et al. Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication. Cell Host Microbe 2018, 23, 254–265.e257. [Google Scholar] [CrossRef]
- Rasmussen, S.B.; Jensen, S.B.; Nielsen, C.; Quartin, E.; Kato, H.; Chen, Z.J.; Silverman, R.H.; Akira, S.; Paludan, S.R. Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene- like receptors, which synergize to induce type I interferon production. J. Gen. Virol. 2009, 90, 74–78. [Google Scholar] [CrossRef]
- Ablasser, A.; Bauernfeind, F.; Hartmann, G.; Latz, E.; Fitzgerald, K.A.; Hornung, V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat. Immunol. 2009, 10, 1065–1072. [Google Scholar] [CrossRef] [PubMed]
- Chiu, Y.-H.; MacMillan, J.B.; Chen, Z.J. RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway. Cell 2009, 138, 576–591. [Google Scholar] [CrossRef] [PubMed]
- Robinson, E.K.; Jagannatha, P.; Covarrubias, S.; Cattle, M.; Smaliy, V.; Safavi, R.; Shapleigh, B.; Abu-Shumays, R.; Jain, M.; Cloonan, S.M.; et al. Inflammation drives alternative first exon usage to regulate immune genes including a novel iron-regulated isoform of Aim2. eLife 2021, 10, e69431. [Google Scholar] [CrossRef] [PubMed]
- Hamel, R.; Dejarnac, O.; Wichit, S.; Ekchariyawat, P.; Neyret, A.; Luplertlop, N.; Perera-Lecoin, M.; Surasombatpattana, P.; Talignani, L.; Thomas, F.; et al. Biology of Zika Virus Infection in Human Skin Cells. J. Virol. 2015, 89, 8880–8896. [Google Scholar] [CrossRef] [PubMed]
- Ekchariyawat, P.; Hamel, R.; Bernard, E.; Wichit, S.; Surasombatpattana, P.; Talignani, L.; Thomas, F.; Choumet, V.; Yssel, H.; Desprès, P.; et al. Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts. Infect. Genet. Evol. 2015, 32, 401–408. [Google Scholar] [CrossRef]
- Qian, F.; Chung, L.; Zheng, W.; Bruno, V.; Alexander, R.P.; Wang, Z.; Wang, X.; Kurscheid, S.; Zhao, H.; Fikrig, E.; et al. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5, 1664–1681. [Google Scholar] [CrossRef]
- Yogarajah, T.; Ong, K.C.; Perera, D.; Wong, K.T. AIM2 Inflammasome-Mediated Pyroptosis in Enterovirus A71-Infected Neuronal Cells Restricts Viral Replication. Sci. Rep. 2017, 7, 5845. [Google Scholar] [CrossRef]
- Li, N.; Parrish, M.; Chan, T.K.; Yin, L.; Rai, P.; Yoshiyuki, Y.; Abolhassani, N.; Tan, K.B.; Kiraly, O.; Chow, V.T.K.; et al. Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration. Cell. Mol. Life Sci. 2015, 72, 2973–2988. [Google Scholar] [CrossRef]
- Mansell, A.; Tate, M.D. In Vivo Infection Model of Severe Influenza A Virus. Methods Mol. Biol. 2018, 1725, 91–99. [Google Scholar] [CrossRef]
- Marois, I.; Cloutier, A.; Garneau, É.; Richter, M.V. Initial infectious dose dictates the innate, adaptive, and memory responses to influenza in the respiratory tract. J. Leukoc. Biol. 2012, 92, 107–121. [Google Scholar] [CrossRef]
- Oltean, T.; Maelfait, J.; Saelens, X.; Vandenabeele, P. Need for standardization of Influenza A virus-induced cell death in vivo to improve consistency of inter-laboratory research findings. Cell Death Discov. 2024, 10, 247. [Google Scholar] [CrossRef] [PubMed]
- Moriyama, M.; Nagai, M.; Maruzuru, Y.; Koshiba, T.; Kawaguchi, Y.; Ichinohe, T. Influenza Virus-Induced Oxidized DNA Activates Inflammasomes. iScience 2020, 23, 101270. [Google Scholar] [CrossRef] [PubMed]
- Combs, J.A.; Norton, E.B.; Saifudeen, Z.R.; Bentrup, K.H.Z.; Katakam, P.V.; Morris, C.A.; Myers, L.; Kaur, A.; Sullivan, D.E.; Zwezdaryk, K.J. Human Cytomegalovirus Alters Host Cell Mitochondrial Function during Acute Infection. J. Virol. 2020, 94, e01183-19. [Google Scholar] [CrossRef]
- Costa, T.J.; Potje, S.R.; Fraga-Silva, T.F.C.; da Silva-Neto, J.A.; Barros, P.R.; Rodrigues, D.; Machado, M.R.; Martins, R.B.; Santos-Eichler, R.A.; Benatti, M.N.; et al. Mitochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damage. Vasc. Pharmacol. 2022, 142, 106946. [Google Scholar] [CrossRef]
- He, W.-R.; Cao, L.-B.; Yang, Y.-L.; Hua, D.; Hu, M.-M.; Shu, H.-B. VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release. Cell. Mol. Immunol. 2021, 18, 1186–1196. [Google Scholar] [CrossRef]
- Moriyama, M.; Koshiba, T.; Ichinohe, T. Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses. Nat. Commun. 2019, 10, 4624. [Google Scholar] [CrossRef]
- Sun, B.; Sundström, K.B.; Chew, J.J.; Bist, P.; Gan, E.S.; Tan, H.C.; Goh, K.C.; Chawla, T.; Tang, C.K.; Ooi, E.E. Dengue virus activates cGAS through the release of mitochondrial DNA. Sci. Rep. 2017, 7, 3594. [Google Scholar] [CrossRef]
- Xu, X.; Cai, J.; Wang, X.; Lu, Y.; Guo, B.; Lai, M.; Lan, L.; Peng, Y.; Zheng, X. Human cytomegalovirus infection activates NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP-1 cells. Microbiol. Immunol. 2023, 67, 303–313. [Google Scholar] [CrossRef] [PubMed]
- Jeon, H.; Lee, J.; Lee, S.; Kang, S.K.; Park, S.J.; Yoo, S.M.; Lee, M.S. Extracellular Vesicles From KSHV-Infected Cells Stimulate Antiviral Immune Response Through Mitochondrial DNA. Front. Immunol. 2019, 10, 876. [Google Scholar] [CrossRef]
- West, A.P.; Khoury-Hanold, W.; Staron, M.; Tal, M.C.; Pineda, C.M.; Lang, S.M.; Bestwick, M.; Duguay, B.A.; Raimundo, N.; MacDuff, D.A.; et al. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520, 553–557. [Google Scholar] [CrossRef]
- Dang, E.V.; McDonald, J.G.; Russell, D.W.; Cyster, J.G. Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation. Cell 2017, 171, 1057–1071.e1011. [Google Scholar] [CrossRef] [PubMed]
- Guo, M.M.; Huang, Y.H.; Wang, F.S.; Chang, L.S.; Chen, K.D.; Kuo, H.C. CD36 is Associated With the Development of Coronary Artery Lesions in Patients with Kawasaki Disease. Front. Immunol. 2022, 13, 790095. [Google Scholar] [CrossRef] [PubMed]
- Weindel, C.G.; Martinez, E.L.; Zhao, X.; Mabry, C.J.; Bell, S.L.; Vail, K.J.; Coleman, A.K.; VanPortfliet, J.J.; Zhao, B.; Wagner, A.R.; et al. Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis. Cell 2022, 185, 3214–3231.e3223. [Google Scholar] [CrossRef] [PubMed]
- Arneth, B. Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects. Front. Immunol. 2019, 10, 1697. [Google Scholar] [CrossRef] [PubMed]
- Shao, W.H.; Cohen, P.L. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res. Ther. 2011, 13, 202. [Google Scholar] [CrossRef]
- Narasaraju, T.; Yang, E.; Samy, R.P.; Ng, H.H.; Poh, W.P.; Liew, A.A.; Phoon, M.C.; van Rooijen, N.; Chow, V.T. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am. J. Pathol. 2011, 179, 199–210. [Google Scholar] [CrossRef]
- Zhu, L.; Liu, L.; Zhang, Y.; Pu, L.; Liu, J.; Li, X.; Chen, Z.; Hao, Y.; Wang, B.; Han, J.; et al. High Level of Neutrophil Extracellular Traps Correlates with Poor Prognosis of Severe Influenza A Infection. J. Infect. Dis. 2018, 217, 428–437. [Google Scholar] [CrossRef]
- Kim, S.J.; Carestia, A.; McDonald, B.; Zucoloto, A.Z.; Grosjean, H.; Davis, R.P.; Turk, M.; Naumenko, V.; Antoniak, S.; Mackman, N.; et al. Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology during Severe Influenza Infection. Front. Immunol. 2021, 12, 772859. [Google Scholar] [CrossRef]
- Zafarani, A.; Razizadeh, M.H.; Haghi, A. Neutrophil extracellular traps in influenza infection. Heliyon 2023, 9, e23306. [Google Scholar] [CrossRef]
- Li, H.; Li, Y.; Song, C.; Hu, Y.; Dai, M.; Liu, B.; Pan, P. Neutrophil Extracellular Traps Augmented Alveolar Macrophage Pyroptosis via AIM2 Inflammasome Activation in LPS-Induced ALI/ARDS. J. Inflamm. Res. 2021, 14, 4839–4858. [Google Scholar] [CrossRef]
- Sun, L.; Wu, J.; Du, F.; Chen, X.; Chen, Z.J. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science 2013, 339, 786–791. [Google Scholar] [CrossRef] [PubMed]
- Wu, J.; Sun, L.; Chen, X.; Du, F.; Shi, H.; Chen, C.; Chen, Z.J. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science 2013, 339, 826–830. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, Y.; Chen, Z.J. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal 2012, 5, ra20. [Google Scholar] [CrossRef] [PubMed]
- Swanson, K.V.; Junkins, R.D.; Kurkjian, C.J.; Holley-Guthrie, E.; Pendse, A.A.; El Morabiti, R.; Petrucelli, A.; Barber, G.N.; Benedict, C.A.; Ting, J.P.Y. A noncanonical function of cGAMP in inflammasome priming and activation. J. Exp. Med. 2017, 214, 3611–3626. [Google Scholar] [CrossRef]
- Zhang, T.; Yin, C.; Boyd, D.F.; Quarato, G.; Ingram, J.P.; Shubina, M.; Ragan, K.B.; Ishizuka, T.; Crawford, J.C.; Tummers, B.; et al. Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis. Cell 2020, 180, 1115–1129.e1113. [Google Scholar] [CrossRef] [PubMed]
- Takaoka, A.; Wang, Z.; Choi, M.K.; Yanai, H.; Negishi, H.; Ban, T.; Lu, Y.; Miyagishi, M.; Kodama, T.; Honda, K.; et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007, 448, 501–505. [Google Scholar] [CrossRef]
- Kesavardhana, S.; Malireddi, R.K.S.; Burton, A.R.; Porter, S.N.; Vogel, P.; Pruett-Miller, S.M.; Kanneganti, T.D. The Zα2 domain of ZBP1 is a molecular switch regulating influenza-induced PANoptosis and perinatal lethality during development. J. Biol. Chem. 2020, 295, 8325–8330. [Google Scholar] [CrossRef]
- Zheng, M.; Kanneganti, T.D. The regulation of the ZBP1-NLRP3 inflammasome and its implications in pyroptosis, apoptosis, and necroptosis (PANoptosis). Immunol. Rev. 2020, 297, 26–38. [Google Scholar] [CrossRef]
- Kuriakose, T.; Man, S.M.; Malireddi, R.K.; Karki, R.; Kesavardhana, S.; Place, D.E.; Neale, G.; Vogel, P.; Kanneganti, T.D. ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways. Sci. Immunol. 2016, 1, aag2045. [Google Scholar] [CrossRef]
- Lee, S.; Karki, R.; Wang, Y.; Nguyen, L.N.; Kalathur, R.C.; Kanneganti, T.D. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 2021, 597, 415–419. [Google Scholar] [CrossRef]
- Thapa, R.J.; Ingram, J.P.; Ragan, K.B.; Nogusa, S.; Boyd, D.F.; Benitez, A.A.; Sridharan, H.; Kosoff, R.; Shubina, M.; Landsteiner, V.J.; et al. DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death. Cell Host Microbe 2016, 20, 674–681. [Google Scholar] [CrossRef] [PubMed]
- Miller, J.L.; Anders, E.M. Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells. J. Gen. Virol. 2003, 84, 193–202. [Google Scholar] [CrossRef] [PubMed]
- Hale, B.G.; Randall, R.E.; Ortín, J.; Jackson, D. The multifunctional NS1 protein of influenza A viruses. J. Gen. Virol. 2008, 89, 2359–2376. [Google Scholar] [CrossRef] [PubMed]
- Opitz, B.; Rejaibi, A.; Dauber, B.; Eckhard, J.; Vinzing, M.; Schmeck, B.; Hippenstiel, S.; Suttorp, N.; Wolff, T. IFNβ induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell. Microbiol. 2007, 9, 930–938. [Google Scholar] [CrossRef] [PubMed]
- Guo, Z.; Chen, L.M.; Zeng, H.; Gomez, J.A.; Plowden, J.; Fujita, T.; Katz, J.M.; Donis, R.O.; Sambhara, S. NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I. Am. J. Respir. Cell Mol. Biol. 2007, 36, 263–269. [Google Scholar] [CrossRef] [PubMed]
- Mibayashi, M.; Martínez-Sobrido, L.; Loo, Y.-M.; Cárdenas Washington, B.; Gale, M.; García-Sastre, A. Inhibition of Retinoic Acid-Inducible Gene I-Mediated Induction of Beta Interferon by the NS1 Protein of Influenza A Virus. J. Virol. 2007, 81, 514–524. [Google Scholar] [CrossRef]
- Shah, S.; Bohsali, A.; Ahlbrand, S.E.; Srinivasan, L.; Rathinam, V.A.; Vogel, S.N.; Fitzgerald, K.A.; Sutterwala, F.S.; Briken, V. Cutting edge: Mycobacterium tuberculosis but not nonvirulent mycobacteria inhibits IFN-β and AIM2 inflammasome-dependent IL-1β production via its ESX-1 secretion system. J. Immunol. 2013, 191, 3514–3518. [Google Scholar] [CrossRef] [PubMed]
- Kaminski, J.J.; Schattgen, S.A.; Tzeng, T.C.; Bode, C.; Klinman, D.M.; Fitzgerald, K.A. Synthetic oligodeoxynucleotides containing suppressive TTAGGG motifs inhibit AIM2 inflammasome activation. J. Immunol. 2013, 191, 3876–3883. [Google Scholar] [CrossRef]
- Steinhagen, F.; Zillinger, T.; Peukert, K.; Fox, M.; Thudium, M.; Barchet, W.; Putensen, C.; Klinman, D.; Latz, E.; Bode, C. Suppressive oligodeoxynucleotides containing TTAGGG motifs inhibit cGAS activation in human monocytes. Eur. J. Immunol. 2018, 48, 605–611. [Google Scholar] [CrossRef]
- Khare, S.; Ratsimandresy, R.A.; de Almeida, L.; Cuda, C.M.; Rellick, S.L.; Misharin, A.V.; Wallin, M.C.; Gangopadhyay, A.; Forte, E.; Gottwein, E.; et al. The PYRIN domain-only protein POP3 inhibits ALR inflammasomes and regulates responses to infection with DNA viruses. Nat. Immunol. 2014, 15, 343–353. [Google Scholar] [CrossRef]
- Yin, Q.; Sester, D.P.; Tian, Y.; Hsiao, Y.S.; Lu, A.; Cridland, J.A.; Sagulenko, V.; Thygesen, S.J.; Choubey, D.; Hornung, V.; et al. Molecular mechanism for p202-mediated specific inhibition of AIM2 inflammasome activation. Cell Rep. 2013, 4, 327–339. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.-H.; Ye, Z.-W.; Deng, J.-J.; Siu, K.-L.; Gao, W.-W.; Chaudhary, V.; Cheng, Y.; Fung, S.-Y.; Yuen, K.-S.; Ho, T.-H.; et al. Inhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16. EMBO Rep. 2018, 19, e45737. [Google Scholar] [CrossRef] [PubMed]
- Green, J.P.; El-Sharkawy, L.Y.; Roth, S.; Zhu, J.; Cao, J.; Leach, A.G.; Liesz, A.; Freeman, S.; Brough, D. Discovery of an inhibitor of DNA-driven inflammation that preferentially targets the AIM2 inflammasome. iScience 2023, 26, 106758. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.; Sooreshjani, M.A.; Mikek, C.; Opoku-Temeng, C.; Sintim, H.O. Suramin potently inhibits cGAMP synthase, cGAS, in THP1 cells to modulate IFN-β levels. Future Med. Chem. 2018, 10, 1301–1317. [Google Scholar] [CrossRef]
- Kusunoki, Y.; Nakazawa, D.; Shida, H.; Hattanda, F.; Miyoshi, A.; Masuda, S.; Nishio, S.; Tomaru, U.; Atsumi, T.; Ishizu, A. Peptidylarginine Deiminase Inhibitor Suppresses Neutrophil Extracellular Trap Formation and MPO-ANCA Production. Front. Immunol. 2016, 7, 227. [Google Scholar] [CrossRef]
- Lewis, H.D.; Liddle, J.; Coote, J.E.; Atkinson, S.J.; Barker, M.D.; Bax, B.D.; Bicker, K.L.; Bingham, R.P.; Campbell, M.; Chen, Y.H.; et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat. Chem. Biol. 2015, 11, 189–191. [Google Scholar] [CrossRef]
- Knight, J.S.; Subramanian, V.; O’Dell, A.A.; Yalavarthi, S.; Zhao, W.; Smith, C.K.; Hodgin, J.B.; Thompson, P.R.; Kaplan, M.J. Peptidylarginine deiminase inhibition disrupts NET formation and protects against kidney, skin and vascular disease in lupus-prone MRL/lpr mice. Ann. Rheum. Dis. 2015, 74, 2199–2206. [Google Scholar] [CrossRef]
- Zawrotniak, M.; Kozik, A.; Rapala-Kozik, M. Selected mucolytic, anti-inflammatory and cardiovascular drugs change the ability of neutrophils to form extracellular traps (NETs). Acta Biochim. Pol. 2015, 62, 465–473. [Google Scholar] [CrossRef]
- Aruoma, O.I.; Halliwell, B.; Hoey, B.M.; Butler, J. The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic. Biol. Med. 1989, 6, 593–597. [Google Scholar] [CrossRef]
- De Flora, S.; Grassi, C.; Carati, L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur. Respir. J. 1997, 10, 1535. [Google Scholar] [CrossRef]
- Zong, Y.; Li, H.; Liao, P.; Chen, L.; Pan, Y.; Zheng, Y.; Zhang, C.; Liu, D.; Zheng, M.; Gao, J. Mitochondrial dysfunction: Mechanisms and advances in therapy. Signal Transduct. Target. Ther. 2024, 9, 124. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Ahn, H.; Han, B.-C.; Shin, H.; Kim, J.-C.; Jung, E.-M.; Kim, J.; Yang, H.; Lee, J.; Kang, S.G.; et al. Obovatol inhibits NLRP3, AIM2, and non-canonical inflammasome activation. Phytomedicine 2019, 63, 153019. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Cao, Y.; Dang, C.; Han, B.; Han, R.; Ma, H.; Hao, J.; Wang, L. Inhibition of double-strand DNA-sensing cGAS ameliorates brain injury after ischemic stroke. EMBO Mol. Med. 2020, 12, e11002. [Google Scholar] [CrossRef]
- MacKenzie, S.H.; Schipper, J.L.; Clark, A.C. The potential for caspases in drug discovery. Curr. Opin. Drug Discov. Dev. 2010, 13, 568. [Google Scholar]
- Dhani, S.; Zhao, Y.; Zhivotovsky, B. A long way to go: Caspase inhibitors in clinical use. Cell Death Dis. 2021, 12, 949. [Google Scholar] [CrossRef]
- Wannamaker, W.; Davies, R.; Namchuk, M.; Pollard, J.; Ford, P.; Ku, G.; Decker, C.; Charifson, P.; Weber, P.; Germann, U.A.; et al. (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J. Pharmacol. Exp. Ther. 2007, 321, 509–516. [Google Scholar] [CrossRef]
- Keller, M.; Sollberger, G.; Beer, H.D. Thalidomide inhibits activation of caspase-1. J. Immunol. 2009, 183, 5593–5599. [Google Scholar] [CrossRef]
- Kast, R.E. Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis, and thereby hasten recovery. Jop 2008, 9, 350–353. [Google Scholar] [PubMed]
- Yang, M.; Fang, J.T.; Zhang, N.S.; Qin, L.J.; Zhuang, Y.Y.; Wang, W.W.; Zhu, H.P.; Zhang, Y.J.; Xia, P.; Zhang, Y. Caspase-1-Inhibitor AC-YVAD-CMK Inhibits Pyroptosis and Ameliorates Acute Kidney Injury in a Model of Sepsis. Biomed. Res. Int. 2021, 2021, 6636621. [Google Scholar] [CrossRef]
- Zorman, J.; Sušjan, P.; Hafner-Bratkovič, I. Shikonin Suppresses NLRP3 and AIM2 Inflammasomes by Direct Inhibition of Caspase-1. PLoS ONE 2016, 11, e0159826. [Google Scholar] [CrossRef]
- Cao, W.; Mishina, M.; Ranjan, P.; De La Cruz, J.A.; Kim, J.H.; Garten, R.; Kumar, A.; García-Sastre, A.; Katz, J.M.; Gangappa, S.; et al. A Newly Emerged Swine-Origin Influenza A(H3N2) Variant Dampens Host Antiviral Immunity but Induces Potent Inflammasome Activation. J. Infect. Dis. 2015, 212, 1923–1929. [Google Scholar] [CrossRef] [PubMed]
- Chan, M.C.; Cheung, C.Y.; Chui, W.H.; Tsao, S.W.; Nicholls, J.M.; Chan, Y.O.; Chan, R.W.; Long, H.T.; Poon, L.L.; Guan, Y.; et al. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. Respir. Res. 2005, 6, 135. [Google Scholar] [CrossRef] [PubMed]
- Short, K.R.; Veeris, R.; Leijten, L.M.; van den Brand, J.M.; Jong, V.L.; Stittelaar, K.; Osterhaus, A.D.M.E.; Andeweg, A.; van Riel, D. Proinflammatory Cytokine Responses in Extra-Respiratory Tissues During Severe Influenza. J. Infect. Dis. 2017, 216, 829–833. [Google Scholar] [CrossRef] [PubMed]
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Xu, D.W.; Tate, M.D. Taking AIM at Influenza: The Role of the AIM2 Inflammasome. Viruses 2024, 16, 1535. https://doi.org/10.3390/v16101535
Xu DW, Tate MD. Taking AIM at Influenza: The Role of the AIM2 Inflammasome. Viruses. 2024; 16(10):1535. https://doi.org/10.3390/v16101535
Chicago/Turabian StyleXu, Dianne W., and Michelle D. Tate. 2024. "Taking AIM at Influenza: The Role of the AIM2 Inflammasome" Viruses 16, no. 10: 1535. https://doi.org/10.3390/v16101535
APA StyleXu, D. W., & Tate, M. D. (2024). Taking AIM at Influenza: The Role of the AIM2 Inflammasome. Viruses, 16(10), 1535. https://doi.org/10.3390/v16101535