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Encephalitozoon cuniculi and Vittaforma corneae (Phylum Microsporidia) inhibit staurosporine-induced apoptosis in human THP-1 macrophages in vitro

Published online by Cambridge University Press:  29 November 2018

Yuliya Y. Sokolova ,
Lisa C. Bowers ,
Xavier Alvarez  and
Elizabeth S. Didier Open the ORCID record for Elizabeth S. Didier [Opens in a new window]
Yuliya Y. Sokolova
Affiliation:
Russian Academy of Sciences, Institute of Cytology, St. Petersburg 194064, Russia Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA
Lisa C. Bowers
Affiliation:
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA
Xavier Alvarez
Affiliation:
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA
Elizabeth S. Didier*
Affiliation:
Division of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USA
*
Author for correspondence: Elizabeth S. Didier, E-mail: [email protected]
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Abstract

Obligately intracellular microsporidia regulate their host cell life cycles, including apoptosis, but this has not been evaluated in phagocytic host cells such as macrophages that can facilitate infection but also can be activated to kill microsporidia. We examined two biologically dissimilar human-infecting microsporidia species, Encephalitozoon cuniculi and Vittaforma corneae, for their effects on staurosporine-induced apoptosis in the human macrophage-differentiated cell line, THP1. Apoptosis was measured after exposure of THP-1 cells to live and dead mature organisms via direct fluorometric measurement of Caspase 3, colorimetric and fluorometric TUNEL assays, and mRNA gene expression profiles using Apoptosis RT2 Profiler PCR Array. Both species of microsporidia modulated the intrinsic apoptosis pathway. In particular, live E. cuniculi spores inhibited staurosporine-induced apoptosis as well as suppressed pro-apoptosis genes and upregulated anti-apoptosis genes more broadly than V. corneae. Exposure to dead spores induced an opposite effect. Vittaforma corneae, however, also induced inflammasome activation via Caspases 1 and 4. Of the 84 apoptosis-related genes assayed, 42 (i.e. 23 pro-apoptosis, nine anti-apoptosis, and 10 regulatory) genes were more affected including those encoding members of the Bcl2 family, caspases and their regulators, and members of the tumour necrosis factor (TNF)/TNF receptor R superfamily.

Keywords

Caspasesimmune evasioninflammationintracellular parasitesopportunistic parasitesTUNEL
Type
Research Article
Information
Parasitology , Volume 146 , Issue 5 , April 2019 , pp. 569 - 579
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Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

Current address: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.

†

Current address: Center for Comparative Medicine, University of California, County Road 98 and Hutchison, Davis, CA 95616, USA.

References

Aoki Mdel, P, Cano, RC, Pellegrini, AV, Tanos, T, Guinazu, NL, Coso, OA and Gea, S (2006) Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein. Microbes and Infection 8, 1723–1731.Google Scholar
Bratton, SB and Salvesen, GS (2010) Regulation of the Apaf-1-caspase-9 apoptosome. Journal of Cell Science 123, 3209–3214.Google Scholar
Bruchhaus, I, Roeder, T, Rennenberg, A and Heussler, VT (2007) Protozoan parasites: programmed cell death as a mechanism of parasitism. Trends Parasitol 23, 376–383.Google Scholar
Cali, A and Takvorian, PM (2014) Developmental morphology and life cycles of the microsporidia. In Weiss, LM and Becnel, JJ (eds), Microsporidia: Pathogens of Opportunity. Hoboken, NJ, USA: John Wiley & Sons, Inc., pp. 71–133.Google Scholar
Channon, JY, Miselis, KA, Minns, LA, Dutta, C and Kasper, LH (2002) Toxoplasma gondii induces granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor secretion by human fibroblasts: implications for neutrophil apoptosis. Infection and Immunity 70, 6048–6057.Google Scholar
Cooks, T, Harris, CC and Oren, M (2014) Caught in the cross fire: p53 in inflammation. Carcinogenesis 35, 1680–1690.Google Scholar
Cuomo, CA, Desjardins, CA, Bakowski, MA, Goldberg, J, Ma, AT, Becnel, JJ, Didier, ES, Fan, L, Heiman, DI, Levin, JZ, Young, S, Zeng, Q and Troemel, ER (2012) Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome Research 22, 2478–2488.Google Scholar
de Hoon, MJL, Imoto, S, Nolan, J and Miyano, S (2004) Open source clustering software. Bioinformatics 20, 1453–1454.Google Scholar
del Aguila, C, Izquierdo, F, Granja, AG, Hurtado, C, Fenoy, S, Fresno, M and Revilla, Y (2006) Encephalitozoon microsporidia modulates p53-mediated apoptosis in infected cells. International Journal for Parasitology 36, 869–876.Google Scholar
Deplazes, P, Mathis, A, van Saanen, M, Iten, A, Keller, R, Tanner, I, Glauser, MP, Weber, R and Canning, EU (1998) Dual microsporidial infection due to Vittaforma corneae and Encephalitozoon hellem in a patient with AIDS. Clinical Infectious Diseases 27, 1521–1524.Google Scholar
Desjardins, CA, Sanscrainte, ND, Goldberg, JM, Heiman, D, Young, S, Zeng, Q, Madhani, HD, Becnel, JJ and Cuomo, CA (2015) Contrasting host-pathogen interactions and genome evolution in two generalist and specialist microsporidian pathogens of mosquitoes. Nature Communications 6, 7121.Google Scholar
Dessauge, F, Lizundia, R, Baumgartner, M, Chaussepied, M and Langsley, G (2005) Taking the Myc is bad for Theileria. Trends Parasitol 21, 377–385.Google Scholar
Didier, ES and Weiss, LM (2006) Microsporidiosis: current status. Current Opinion in Infectious Diseases 19, 485–492.Google Scholar
Didier, ES, Bowers, LC, Martin, AD, Kuroda, MJ, Khan, IA and Didier, PJ (2010) Reactive nitrogen and oxygen species, and iron sequestration contribute to macrophage-mediated control of Encephalitozoon cuniculi (Phylum Microsporidia) infection in vitro and in vivo. Microbes and Infection 12, 1244–1251.Google Scholar
Eisen, MB, Spellman, PT, Brown, PO and Botstein, D (1998) Cluster analysis and display of genome-wide expression patterns. Proceedings of the National Academy of Sciences of the USA 95, 14863–14868.Google Scholar
Faherty, CS and Maurelli, AT (2008) Staying alive: bacterial inhibition of apoptosis during infection. Trends in Microbiology 16, 173–180.Google Scholar
Ferguson, S and Lucocq, J (2018) The invasive cell coat at the microsporidian Trachipleistophora hominis-host cell interface contains secreted hexokinases. Microbiologyopen e00696. doi: 10.1002/mbo3.696.Google Scholar
Fridman, JS and Lowe, SW (2003) Control of apoptosis by p53. Oncogene 22, 9030–9040.Google Scholar
Goebel, S, Gross, U and Luder, CG (2001) Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression. Journal of Cell Science 114, 3495–3505.Google Scholar
Graumann, K, Hippe, D, Gross, U and Luder, CG (2009) Mammalian apoptotic signalling pathways: multiple targets of protozoan parasites to activate or deactivate host cell death. Microbes and Infection 11, 1079–1087.Google Scholar
Hay, S and Kannourakis, G (2002) A time to kill: viral manipulation of the cell death program. Journal of General Virology 83, 1547–1564.Google Scholar
He, X, Fu, Z, Li, M, Liu, H, Cai, S, Man, N and Lu, X (2015) Nosema bombycis (Microsporidia) suppresses apoptosis in BmN cells (Bombyx mori). Acta Biochim Biophys Sin (Shanghai) 47, 696–702.Google Scholar
Hehlgans, T and Pfeffer, K (2005) The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 115, 1–20.Google Scholar
Heinz, E, Hacker, C, Dean, P, Mifsud, J, Goldberg, AV, Williams, TA, Nakjang, S, Gregory, A, Hirt, RP, Lucocq, JM, Kunji, ER and Embley, TM (2014) Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites. PLoS Pathogens 10, e1004547.Google Scholar
Higes, M, Juarranz, A, Dias-Almeida, J, Lucena, S, Botias, C, Meana, A, Garcia-Palencia, P and Martin-Hernandez, R (2013) Apoptosis in the pathogenesis of Nosema ceranae (Microsporidia: Nosematidae) in honey bees (Apis mellifera). Environmental Microbiology Reports 5, 530–536.Google Scholar
Huang, Q, Chen, YP, Wang, RW, Cheng, S and Evans, JD (2016) Host-parasite interactions and purifying selection in a microsporidian parasite of honey bees. PLoS ONE 11, e0147549.Google Scholar
James, ER and Green, DR (2004) Manipulation of apoptosis in the host-parasite interaction. Trends in Parasitology 20, 280–287.Google Scholar
Kurze, C, Le Conte, Y, Dussaubat, C, Erler, S, Kryger, P, Lewkowski, O, Muller, T, Widder, M and Moritz, RF (2015) Nosema tolerant honeybees (Apis mellifera) escape parasitic manipulation of apoptosis. PLoS ONE 10, e0140174.Google Scholar
Kurze, C, Dosselli, R, Grassl, J, Le Conte, Y, Kryger, P, Baer, B and Moritz, RF (2016) Differential proteomics reveals novel insights into Nosema-honey bee interactions. Insect Biochemistry and Insect Molecular Biology 79, 42–49.Google Scholar
Leitch, GJ, Shaw, AP, Colden-Stanfield, M, Scanlon, M and Visvesvara, GS (2005) Multinucleate host cells induced by Vittaforma corneae (Microsporidia). Folia Parasitol (Praha) 52, 103–110.Google Scholar
Liu, J, Deng, M, Lancto, CA, Abrahamsen, MS, Rutherford, MS and Enomoto, S (2009) Biphasic modulation of apoptotic pathways in Cryptosporidium parvum-infected human intestinal epithelial cells. Infection and Immunity 77, 837–849.Google Scholar
Locksley, RM, Killeen, N and Lenardo, MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487–501.Google Scholar
Luallen, RJ, Bakowski, MA and Troemel, ER (2015) Characterization of microsporidia-induced developmental arrest and a transmembrane leucine-rich repeat protein in Caenorhabditis elegans. PLoS ONE 10, e0124065.Google Scholar
Luder, CG, Gross, U and Lopes, MF (2001) Intracellular protozoan parasites and apoptosis: diverse strategies to modulate parasite-host interactions. Trends Parasitol 17, 480–486.Google Scholar
Luo, X, Budihardjo, I, Zou, H, Slaughter, C and Wang, X (1998) Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481–490.Google Scholar
Martin-Hernandez, R, Higes, M, Sagastume, S, Juarranz, A, Dias-Almeida, J, Budge, GE, Meana, A and Boonham, N (2017) Microsporidia infection impacts the host cell's cycle and reduces host cell apoptosis. PLoS ONE 12, e0170183.Google Scholar
Menendez, D, Shatz, M, Azzam, K, Garantziotis, S, Fessler, MB and Resnick, MA (2011) The Toll-like receptor gene family is integrated into human DNA damage and p53 networks. PLoS Genetics 7, e1001360.Google Scholar
Molestina, RE, Payne, TM, Coppens, I and Sinai, AP (2003) Activation of NF-kappaB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IkappaB to the parasitophorous vacuole membrane. Journal of Cell Science 116, 4359–4371.Google Scholar
Orlofsky, A, Weiss, LM, Kawachi, N and Prystowsky, MB (2002) Deficiency in the anti-apoptotic protein A1-a results in a diminished acute inflammatory response. The Journal of Immunology 168, 1840–1846.Google Scholar
Panek, J, El Alaoui, H, Mone, A, Urbach, S, Demettre, E, Texier, C, Brun, C, Zanzoni, A, Peyretaillade, E, Parisot, N, Lerat, E, Peyret, P, Delbac, F and Biron, DG (2014) Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae. PLoS ONE 9, e100791.Google Scholar
Payne, TM, Molestina, RE and Sinai, AP (2003) Inhibition of caspase activation and a requirement for NF-kappaB function in the Toxoplasma gondii-mediated blockade of host apoptosis. Journal of Cell Science 116, 4345–4358.Google Scholar
Peyretaillade, E, El Alaoui, H, Diogon, M, Polonais, V, Parisot, N, Biron, DG, Peyret, P and Delbac, F (2011) Extreme reduction and compaction of microsporidian genomes. Research in Microbiology 162, 598–606.Google Scholar
Ruhland, A, Leal, N and Kima, PE (2007) Leishmania promastigotes activate PI3K/Akt signalling to confer host cell resistance to apoptosis. Cellular Microbiology 9, 84–96.Google Scholar
Saldanha, AJ (2004) Java Treeview – extensible visualization of microarray data. Bioinformatics 20, 3246–3248.Google Scholar
Scanlon, M, Leitch, GJ, Shaw, AP, Moura, H and Visvesvara, GS (1999) Susceptibility to apoptosis is reduced in the Microsporidia-infected host cell. Journal of Eukaryotic Microbiology 46, 34s–35s.Google Scholar
Scanlon, M, Shaw, AP, Zhou, CJ, Visvesvara, GS and Leitch, GJ (2000) Infection by microsporidia disrupts the host cell cycle. Journal of Eukaryotic Microbiology 47, 525–531.Google Scholar
Senderskiy, IV, Timofeev, SA, Seliverstova, EV, Pavlova, OA and Dolgikh, VV (2014) Secretion of Antonospora (Paranosema) locustae proteins into infected cells suggests an active role of microsporidia in the control of host programs and metabolic processes. PLoS ONE 9, e93585.Google Scholar
Snowden, KF and Shadduck, JA (1999) Microsporidia in higher vertebrates. In Wittner, M and Weiss, LM (eds), The Microsporidia and Microsporidiosis. Washington, DC, USA: ASM Press, pp. 393–417.Google Scholar
Sokolova, YY, Sakaguchi, K and Paulsen, DB (2016) Establishing a new species Encephalitozoon pogonae for the microsporidian parasite of inland bearded dragon Pogona vitticeps Ahl 1927 (Reptilia, Squamata, Agamidae). Journal of Eukaryotic Microbiology 63, 524–535.Google Scholar
Sollberger, G, Strittmatter, GE, Kistowska, M, French, LE and Beer, HD (2012) Caspase-4 is required for activation of inflammasomes. Journal of Immunology 188, 1992–2000.Google Scholar
Stentiford, GD, Bateman, KS, Feist, SW, Oyarzun, S, Uribe, JC, Palacios, M and Stone, DM (2014) Areospora rohanae n.gen. n.sp. (Microsporidia; Areosporiidae n. fam.) elicits multi-nucleate giant-cell formation in southern king crab (Lithodes santolla). Journal of Invertebrate Pathology 118, 1–11.Google Scholar
Timofeev, SA, Tokarev, YS, Simakova, AV, Tsarev, AA and Dolgikh, VV (2016) Interactions of microsporidia with infected host cell. Tsitologiia 58, 594–601.Google Scholar
Watson, AK, Williams, TA, Williams, BA, Moore, KA, Hirt, RP and Embley, TM (2015) Transcriptomic profiling of host-parasite interactions in the microsporidian Trachipleistophora hominis. BMC Genomics 16, 983.Google Scholar
Weiss, LM (2014) Clinical syndromes associated with microsporidiosis. In Weiss, LM and Becnel, JJ (eds), Microsporidia: Pathogens of Opportunity. Hoboken, NJ, USA: John Wiley & Sons, Inc., pp. 371–401.Google Scholar
Wiredu Boakye, D, Jaroenlak, P, Prachumwat, A, Williams, TA, Bateman, KS, Itsathitphaisarn, O, Sritunyalucksana, K, Paszkiewicz, KH, Moore, KA, Stentiford, GD and Williams, BAP (2017) Decay of the glycolytic pathway and adaptation to intranuclear parasitism within Enterocytozoonidae microsporidia. Environmental Microbiology 19, 2077–2089.Google Scholar
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