Skip to main content Accessibility help
×
Home

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

  • T.T.W. Chen (a1) (a2), P.C. Cheng (a3), K.C. Chang (a4), J.P. Cao (a2), J.L. Feng (a4) (a5), C.C. Chen (a4) (a6), H.Y.P. Lam (a1) and S.Y. Peng (a1)...

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.

Copyright

Corresponding author

Author for correspondence: S.Y. Peng, E-mail: pengsy@mail.tcu.edu.tw

Footnotes

Hide All
*

These authors contributed equally to this work

Footnotes

References

Hide All
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.
Andrade, ZA (2009) Schistosomiasis and liver fibrosis. Parasite Immunology 31, 656663.
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.
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.
Boros, DL (1989) Immunopathology of Schistosoma mansoni infection. Clinical Microbiology Reviews 2, 250269.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kanneganti, TD (2010) Central roles of NLRs and inflammasomes in viral infection. Nature Reviews Immunology 10, 688698.
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.
Kawai, T and Akira, S (2010) The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nature Immunology 11, 373384.
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.
Lamkanfi, M and Dixit, VM (2009) Inflammasomes: guardians of cytosolic sanctity. Immunological Reviews 227, 95105.
Lamkanfi, M and Dixit, VM (2012) Inflammasomes and their roles in health and disease. Annual Review of Cell and Developmental Biology 28, 137161.
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.
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.
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.
Martinon, F (2010) Signaling by ROS drives inflammasome activation. European Journal of Immunology 40, 616619.
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.
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.
Pearce, EJ and MacDonald, AS (2002) The immunobiology of schistosomiasis. Nature Reviews Immunology 2, 499511.
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.
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.
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.
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.
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.
Schroder, K and Tschopp, J (2010) The inflammasomes. Cell 140, 821832.
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.
WHO (2017) Schistosomiasis. Available at https://www.who.int/schistosomiasis/en/.
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.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed