Hostname: page-component-848d4c4894-r5zm4 Total loading time: 0 Render date: 2024-07-03T08:30:41.219Z Has data issue: false hasContentIssue false

Activation of the NLRP3 and AIM2 inflammasomes in a mouse model of Schistosoma mansoni infection

Published online by Cambridge University Press:  15 August 2019

T.T.W. Chen
Affiliation:
Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory of Parasite and Vector Biology, MOH, Shanghai 200025, China
P.C. Cheng
Affiliation:
Department of Parasitology and Center for International Tropical medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
K.C. Chang
Affiliation:
Institute of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
J.P. Cao
Affiliation:
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Key Laboratory of Parasite and Vector Biology, MOH, Shanghai 200025, China
J.L. Feng
Affiliation:
Institute of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan Department of Laboratory, Chung-Kang Branch, Cheng-Ching General Hospital, Taichung 40764, Taiwan
C.C. Chen
Affiliation:
Institute of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan Department of Laboratory Medicine, Taipei Medical University-Shuang-Ho Hospital, New Taipei City 23561, Taiwan
H.Y.P. Lam
Affiliation:
Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
S.Y. Peng*
Affiliation:
Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
*
Author for correspondence: S.Y. Peng, E-mail: pengsy@mail.tcu.edu.tw

Abstract

Schistosomiasis is an inflammatory disease that occurs when schistosome species eggs are deposited in the liver, resulting in fibrosis and portal hypertension. Schistosomes can interact with host inflammasomes to elicit host immune responses, leading to mitochondrial damage, generation of high levels of reactive oxygen species (ROS) and activation of apoptosis during inflammation. This study aims to examine whether ROS and NF-κB (p65) expression elicited other types of inflammasome activation in Schistosoma mansoni-infected mouse livers. We examine the relationship between inflammasome activation, mitochondrial damage and ROS production in mouse livers infected with S. mansoni. We demonstrate a significant release of ROS and superoxides and increased NF-κB (p65) in S. mansoni-infected mouse livers. Moreover, activation of the NLRP3 and AIM2 inflammasomes was triggered by S. mansoni infection. Stimulation of HuH-7 hepatocellular carcinoma cells with soluble egg antigen induced activation of the AIM2 inflammasome pathway. In this study, we demonstrate that S. mansoni infection promotes both NLRP3 and AIM2 inflammasome activation.

Type
Research Paper
Copyright
Copyright © Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These authors contributed equally to this work

References

Allen, JN, Dey, A, Nissly, R, Fraser, J, Yu, S, Balandaram, G, Peters, JM and Hankey-Giblin, PA (2017) Isolation, characterization, and purification of macrophages from tissues affected by obesity-related inflammation. Journal of Visualized Experiments 122, 113.Google Scholar
Andrade, ZA (2009) Schistosomiasis and liver fibrosis. Parasite Immunology 31, 656663.Google Scholar
Arredondo Zamarripa, D, Diaz-Lezama, N, Melendez Garcia, R, Chavez Balderas, J, Adan, N, Ledesma-Colunga, MG, Arnold, E, Clapp, C and Thebault, S (2014) Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress. Frontiers in Cellular Neuroscience 8, 333.Google Scholar
Bauernfeind, FG, Horvath, G, Stutz, A, et al. (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. Journal of Immunology 183, 787791.Google Scholar
Boros, DL (1989) Immunopathology of Schistosoma mansoni infection. Clinical Microbiology Reviews 2, 250269.Google Scholar
Burke, ML, McManus, DP, Ramm, GA, Duke, M, Li, Y, Jones, MK and Gobert, GN (2010) Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis. PLoS Neglected Tropical Diseases 4, e598.Google Scholar
Chang, D, Ramalho, LN, Ramalho, FS, Martinelli, AL and Zucoloto, S (2006) Hepatic stellate cells in human Schistosomiasis mansoni: A comparative immunohistochemical study with liver cirrhosis. Acta Tropica 97, 318323.Google Scholar
Chen, W, Xu, Y, Li, H, Tao, W, Xiang, Y, Huang, B, Niu, J, Zhong, J and Meng, G (2014) HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells. PLoS One 9, e84953.Google Scholar
Chen, TT, Wu, LS, Hsu, PW, Pang, CY, Lee, KM, Cheng, PC and Peng, SY (2015) Mitochondrial dynamics in the mouse liver infected by Schistosoma mansoni. Acta Tropica 148, 1323.Google Scholar
Duan, Y, Gu, X, Zhu, D, et al. (2014) Schistosoma japonicum soluble egg antigens induce apoptosis and inhibit activation of hepatic stellate cells: A possible molecular mechanism. International Journal for Parasitology 44, 217224.Google Scholar
Franchi, L, Eigenbrod, T, Munoz-Planillo, R and Nunez, G (2009) The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nature Immunology 10, 241247.Google Scholar
Fukumoto, J, Fukumoto, I, Parthasarathy, PT, et al. (2013) NLRP3 deletion protects from hyperoxia-induced acute lung injury. American Journal of Physiology: Cell Physiology 305, C182C189.Google Scholar
Heid, ME, Keyel, PA, Kamga, C, Shiva, S, Watkins, SC and Salter, RD (2013) Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. Journal of Immunology 191, 52305238.Google Scholar
Jones, JW, Kayagaki, N, Broz, P, et al. (2010) Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis. Proceedings of the National Academy of Sciences of the United States of America 107, 97719776.Google Scholar
Kalantari, P, DeOliveira, RB, Chan, J, et al. (2014) Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria. Cell Reports 6, 196210.Google Scholar
Kanneganti, TD (2010) Central roles of NLRs and inflammasomes in viral infection. Nature Reviews Immunology 10, 688698.Google Scholar
Kantrow, SP, Taylor, DE, Carraway, MS and Piantadosi, CA (1997) Oxidative metabolism in rat hepatocytes and mitochondria during sepsis. Archives of Biochemistry and Biophysics 345, 278288.Google Scholar
Kawai, T and Akira, S (2010) The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nature Immunology 11, 373384.Google Scholar
Koay, MA, Christman, JW, Segal, BH, Venkatakrishnan, A, Blackwell, TR, Holland, SM and Blackwell, TS (2001) Impaired pulmonary NF-kappaB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice. Infection and Immunity 69, 59915996.Google Scholar
Lamkanfi, M and Dixit, VM (2009) Inflammasomes: guardians of cytosolic sanctity. Immunological Reviews 227, 95105.Google Scholar
Lamkanfi, M and Dixit, VM (2012) Inflammasomes and their roles in health and disease. Annual Review of Cell and Developmental Biology 28, 137161.Google Scholar
Lamkanfi, M, Mueller, JL, Vitari, AC, Misaghi, S, Fedorova, A, Deshayes, K, Lee, WP, Hoffman, HM and Dixit, VM (2009) Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. Journal of Cell Biology 187, 6170.Google Scholar
Layland, LE, Wagner, H and da Costa, CU (2005) Lack of antigen-specific Th1 response alters granuloma formation and composition in Schistosoma mansoni-infected MyD88-/-mice. European Journal of Immunology 35, 32483257.Google Scholar
Llesuy, S, Evelson, P, Gonzalez-Flecha, B, Peralta, J, Carreras, MC, Poderoso, JJ and Boveris, A (1994) Oxidative stress in muscle and liver of rats with septic syndrome. Free Radical Biology & Medicine 16, 445451.Google Scholar
Martinon, F (2010) Signaling by ROS drives inflammasome activation. European Journal of Immunology 40, 616619.Google Scholar
Meng, N, Xia, M, Lu, YQ, Wang, M, Boini, KM, Li, PL and Tang, WX (2016) Activation of NLRP3 inflammasomes in mouse hepatic stellate cells during Schistosoma J. infection. Oncotarget 7, 3931639331.Google Scholar
Nagano, I, Pei, F, Wu, Z, Wu, J, Cui, H, Boonmars, T and Takahashi, Y (2004) Molecular expression of a cysteine proteinase of Clonorchis sinensis and its application to an enzyme-linked immunosorbent assay for immunodiagnosis of clonorchiasis. Clinical and Diagnostic Laboratory Immunology 11, 411416.Google Scholar
Pearce, EJ and MacDonald, AS (2002) The immunobiology of schistosomiasis. Nature Reviews Immunology 2, 499511.Google Scholar
Pearce, EJ, Caspar, P, Grzych, JM, Lewis, FA and Sher, A (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. Journal of Experimental Medicine 173, 159166.Google Scholar
Rathinam, VA, Jiang, Z, Waggoner, SN, et al. (2010) The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nature Immunology 11, 395402.Google Scholar
Ritter, M, Gross, O, Kays, S, Ruland, J, Nimmerjahn, F, Saijo, S, Tschopp, J, Layland, LE and Prazeres da Costa, C (2010) Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proceedings of the National Academy of Sciences of the United States of America 107, 2045920464.Google Scholar
Schramm, G, Gronow, A, Knobloch, J, et al. (2006) IPSE/alpha-1: A major immunogenic component secreted from Schistosoma mansoni eggs. Molecular & Biochemical Parasitology 147, 919.Google Scholar
Schreck, R, Rieber, P and Baeuerle, PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO Journal 10, 22472258.Google Scholar
Schroder, K and Tschopp, J (2010) The inflammasomes. Cell 140, 821832.Google Scholar
Taylor, DE, Ghio, AJ and Piantadosi, CA (1995) Reactive oxygen species produced by liver mitochondria of rats in sepsis. Archives of Biochemistry and Biophysics 316, 7076.Google Scholar
WHO (2017) Schistosomiasis. Available at https://www.who.int/schistosomiasis/en/.Google Scholar
Wynn, TA, Cheever, AW, Jankovic, D, Poindexter, RW, Caspar, P, Lewis, FA and Sher, A (1995) An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 376, 594596.Google Scholar