Differential sensitivity of myeloid and lymphoid cell populations to apoptosis in peritoneal cavity of mice with model larval Mesocestoides vogae infection

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The metacestode stage of the tapeworm Mesocestoides vogae (M. vogae) has the ability of asexual growth in the peritoneal cavity of rodents and other intermediate hosts without restriction. Early immunological events have decisive role in the establishment of infection. In the present study we investigated the kinetic of myeloid and lymphoid cell populations and the proportions of cells undergoing apoptosis in peritoneal cavities of mice within the first month after oral infection with M. vogae larvae. Proportions of cell phenotypes and apoptotic cells were examined by flow cytometry and by microscopical analysis of cells following May/Grünwald staining and fluorescent stain Hoechst 33234, respectively. Total numbers of peritoneal cells increased and their distribution changed towards accumulation of myelo-monocytic cell lineage in the account of reduced proportions of lymphoid cells. CD4+ T cell subpopulations were more abundant than CD8+ and their proportions elevated within two weeks post infection (p.i.) which was followed by a significant decline. Expression level of CD11c marker on myelo-monocytic cells revealed phenotype heterogeneity and proportions of cells with low and medium expression elevated from day 14 p.i. along with concurrent very low presence of CD11chigh phenotype. Lymphoid cell population was highly resistant to apoptosis but elevated proportions of myeloid cells were in early/late stage of apoptosis. Apoptosis was detected in a higher number of adherent cells from day 14 p.i. onwards as evidenced by nuclear fluorescent staining. By contrast, cells adherent to larvae, mostly macrophages and eosinophils, did not have fragmented nuclei. Our data demonstrated that apoptosis did not account for diminished population of peritoneal lymphoid cells and substantial proportions of myeloid cells seem to be more susceptible to apoptotic turnover in peritoneal cavity of mice with ongoing M. vogae infection, suggesting their important role in the host-parasite interactions.

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  • Boyce W. Shender L. Schultz L. Vickers W. Johnson C. Z iccardi M. Beckett L. Padgett K. C rosbie P. Sykes J. (2011): Survival analysis of dogs diagnosed with canine peritoneal larval cestodiasis (Mesocestoides spp.). Vet Parasitol.180(3-4) : 256 – 261. DOI: 10.1016/j.vetpar.2011.03.023

  • Brombacher F. Arendse B. Peterson R. Hölscher A. Hölsher C. (2009): Analyzing classical and alternative macrophage activation in macrophage/neutrophil-specific IL-4 receptor-alpha-deficient mice. Methods Mol. Biol. 531: 225 – 252. DOI: 10.1007/978-1-59745-396-7_15

  • Composto G. Gonzalez D. Bucknum A. Silberman D. Taylor J. Kozlowski M. Bloomfield T. Bartlett T. Riggs J. (2011) Peritoneal T lymphocyte regulation by macrophages. Immunobiology 216(1-2): 256 – 264. DOI: 10.1016/j.imbio.2010.04.002

  • Cook R.M. Ashworth R.F. Chernin J. (1988): Cytotoxic activity of rat granulocytes against Mesocestoides corti. Parasite Immunol. 10(1): 97 – 109

  • Eid Bou Ghosn E. Cassado A.A. Govoni G.R. Fukuhara T. Yang Y. Monack D.M. Bortoluci K.R. Almeida S.R. Herzenberg L.A. Herzenberg L.A. (2010): Two physically functionally and developmentally distinct peritoneal macrophage subsets. Proc. Natl. Acad Sci USA 107(6): 2568 – 2573. DOI: 10.1073/pnas.0915000107.

  • Eleni C. Scaramozzino P. Busi M. Ingrosso S. D’Amelio S. De Liberato C. (2007): Proliferative peritoneal and pleural cestodiasis in a cat caused by metacestodes of Mesocestoides sp. Anatomohistopathological findings and genetic identification. Parasite 14(1): 71 – 76. DOI: 10.1051/parasite/2007141071

  • Gordon S. Martinez F.O.(2010): Alternative activation of macrophages: mechanism and functions. Immunity. 32(5): 593 – 604. DOI: 10.1016/j.immuni.2010.05.007

  • Hrčková G. Velebný S. (1997): Effect of praziquantel and liposome-incorporated praziquantel on peritoneal macrophage activation in mice infected with Mesocestoides corti tetrathyridia (Cestoda). Parasitology 114(Pt 5): 475 – 482

  • Hrčková G. Velebný S. Daxnerová Z. Solar P. (2006): Praziquantel and liposomized glucan-treatment modulated liver fibrogenesis and mastocytosis in mice infected with Mesocestoides vogae (M. corti Cestoda) tetrathyridia. Parasitology 132(Pt 4): 581 – 594. DOI: 10.1017/S0031182005009364

  • Hrčková G. Vendeľova E. Velebný S. (2016): Phagocytosis in Mesocestoides vogae-induced peritoneal monocytes/macrophages via opsonin-dependent or independent pathways. Helminthologia 53: 3 – 13. DOI: 10.1515/helmin-2015-0062

  • Hrčková G. Velebný S. Kogan G. (2017): Antibody response in mice infected with Mesocestoides vogae (syn. Mesocestoides corti) tetrathyridia after treatment with praziquantel and liposomised glucan. Parasitol. Res. 100(6): 1351 – 1359. DOI: 10.1007/s00436-006-0434-2

  • Hrčková G. Velebný S. Solár P. (2010): Dynamics of hepatic stellate cells collagen types I and III synthesis and gene expression of selected cytokines during hepatic fibrogenesis following Mesocestoides vogae (Cestoda) infection in mice. Int. J. Parasitol. 40(2): 163 – 74. DOI: 10.1016/j.ijpara.2009.06.008

  • Horsnell W.G.C. Brombacher F. (2010): Genes associated with alternatively activated macrophages discretely regulate helminth infection and pathogenesis in experimental mouse models. Immunobiology 215(9-10): 704 – 708. DOI: 10.1016/j.imbio.2010.05.011

  • James E.R. Green D.R. (2004): Manipulation of apoptosis in the host-parasite interaction. Trends Parasitol. 20(6): 280 – 287. DOI: 10.1016/j.pt.2004.04.004

  • Jenkins P. Dixon J.B. Haywood S. Rakha N.K. Carter S.D. (1991): Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma. Parasitology 102: 25 – 132. DOI: 10.1017/S0031182000060431

  • Johnson G.R. Nicholas W.L. Metcalf D. McKenzie I.F. Mitchell G.F. (1979): Peritoneal cell population of mice infected with Mesocestoides corti as a source of eosinophils. Int. Arch. Allergy Appl. Immunol 59(3): 315 – 322. DOI: 10.1159/000232275

  • Lai L. Alaverdi N. Maltais L. Morse H.C (1998): Mouse cell surface antigens: nomenclature and immunophenotyping. J. Immunol. 160(8): 3861 – 3868

  • LanteriG. Di CaroG. CapucchioM.T. GaglioG. ReinaV.Lo Giudice C. ZanetS. Marino F. (2017): Mesocestoidosis and multivisceral tetrathyridiosis in a European cat. Veterinarni Medicina 62: 356 – 362. DOI: 10.17221/6/2017-VETMED

  • Mačák Kubašková T. Mudroňová D. Velebný S. Hrčková G. (2018): The utilisation of human dialyzable leukocyte extract (IMMODIN) as adjuvant in albendazole therapy on mouse model of larval cestode infection: Immunomodulatory and hepatoprotective effects. Int. Immunopharm. 65: 148 – 158. DOI: 10.1016/j.intimp.2018.09.045

  • Maizels R.M. (2010): Parasite immunomodulation and polymorphisms of the immune system. J. Biol. 8(7): 62. DOI: 10.1186/jbiol166

  • Maizels R.M. Hewitson J.P. Smith K.A. (2012): Susceptibility and immunity to helminth parasites. Curr. Opin. Immunol. 24(4): 459 – 466. DOI: 10.1016/j.coi.2012.06.003

  • Martinez F.O. Helming L. Gordon S. (2009): Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27: 451 – 483. DOI: 10.1146/annurev.immunol.021908.132532

  • Mourglia-Ettlin G. Margués J.M. Chabalgoity J.A. Dematteis S. (2011): Early peritoneal immune response during Echinococcus granulosus establishment displays a biphasic behavior. PLoS Negl. Trop. Dis. 5(8):e1293. DOI: 10.1371/journal.pntd.0001293

  • Nono J.K. Pletinckx K. Lutz M.B. Brehm K. (2012): Excretory/secretory products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro. PloS Negl. Trop. Dis. 6 e1516. DOI: 10.1371/journal.pntd.0001516

  • O'Connel A.E. Kerepesi L.A. Vandergrift G.L. Herbert D.R. Van Winkle T.J. Hooper D.C. Pearce E.J. Abraham D. (2009): IL-4(-/-) mice with lethal Mesocestoides corti infections-reduced Th2 cytokines and alternatively activated macrophages. Parasite Immunol. 31: 741 – 749. DOI: 10.1111/j.1365-3024.2009.01151.x

  • Rawat J. Dixon J.B. Macintyre A.R. McGarry H.F. Taylor M.J. (2003): IL-4 dependent resistance to the tapeworm Mesocestoides corti (Cestoda) in mice. Parasite Immunol. 25(11-12): 553 – 557. DOI: 10.1111/j.0141-9838.2004.00666.x

  • Rodriguez-Sosa M. Satoskar A.R. Calderón R. Gomez-Garcia L. Saavedra R. Bojalil R. Terrazas L.I. (2002): Chronic helminth infection induces alternatively activated macrophages expressing high levels of CCR5 with low interleukin-12 production and Th2-biasing ability. Infect. Immun. 70(7): 3656 – 3664. DOI: 10.1128/IAI.70.7.3656-3664.2002

  • Selvarajan K. Moldovan L. Chandrakala A.N. Litvinov D. Parthasarathy S. (2011): Peritoneal macrophages are distinct from monocytes and adherent macrophages. Atherosclerosis 219(2): 475-83. DOI: 10.1016/j.atherosclerosis.2011.09.014

  • Serradell M.C. Guasconi L. Cervi L. Chiapello L.S. Masih D.T. (2007): Excretory-secretory products from Fasciola hepatica induce eosinophil apoptosis by a caspase-dependent mechanism. Vet. Immunol. Immunopathol. 117: 197 – 208. DOI: 10.1016/j.vetimm.2007.03.007

  • Singh-Jasuja H. Thiolat A. Ribon M. Boissier M.C. Bessis N. Rammensee H.G. Decker P. (2013): The mouse dendritic cell marker CD11c is down-regulated upon cell activation through Toll-like receptor triggering. Immunobiology 218(1): 28 – 39. DOI: 10.1016/j.imbio.2012.01.021

  • Smith K.A. Hochweller K. Hämmerling G.J. Boon L. MacDonald A.S. Maizels R.M. (2011): Chronic helminth infection promotes immune reagulation in vivo through dominance of CD11cioCD103-dendritic cells. J. Immunol. 168(12): 7098 – 7109. DOI: 10.4049/jimmunol.1003636

  • Solano S. Cortes I. M. Copitin N.I. Tato P. Molinari J.L. (2006): Lymphocyte apoptosis in the inflammatory reaction around Taenia solium metacestode in porcine cysticercosis. Vet. Parasitol. 140: 171 – 176. DOI:10.1016/j.vetpar.2006.03.006

  • Specht D. Voge M. (1965): Asexual multiplication of Mesocestoides tetrarhyridia in laboratory animals. J. Parasitol. 51(2): 268 – 272

  • Specht D. Widmer E.A. (1972): Response of mouse liver to infection with tetrathyridia of Mesocestoides (Cestoda). J. Parasitol. 58(3): 431 – 437. DOI: 10.2307/3278183

  • Spotin A. Mokhtari M. Majdi A. Sankian M. Varasteh A. (2012): The study of apoptotic bifunctional effects in relationship between host and parasite in cystic echinococcosis: a new approach to suppression and survival of hydatid cyst. Parasitol. Res. 110(5): 1979 – 1984. DOI: 10.1007/s00436-011-2726-4.

  • Terrazas C.A. Gómez-Garcia L. Terrazas L.I. (2010): Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling. Int.J. Parasitol. 40(9): 1051 – 1062. DOI: 10.1016/j.ijpara.2010.02.016.

  • Toplu N. Yildiz K. Tunay R. (2004): Massive cystic tetrathyridiosis in a dog. J. Small Anim. Pract. 45(8): 410 – 412. DOI: 10.1111/j.1748-5827.2004.tb00257.x.

  • Velebný S. Hrčkova G. Königová A. (2010). Reduction of oxidative stress and liver injury following silymarin and praziquantel treatment in mice with Mesocestoides vogae (Cestoda) infection. Parasitol. Int. 59: 524 – 531. DOI:10.1016/j.parint.2010.06.012

  • Vendelova E. Lutz M.B. Hrčková G. (2015): Immunity and immune modulation elicited by the larval cestode Mesocestoides vogae and its products. Parasite Immunol. 37: 493 – 504. DOI: 10.1111/pim.12216

  • Vendelova E. Hrčková G. Lutz M.B. Brehm K. Nono Komguep J. (2016a): In vitro culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory-secretory products. Parasite Immunol. 38(7): 403 – 413. DOI: 10.1111/pim.12327

  • Vendelova E. Camargo de L.J. Lorenzatto K.R. Monteiro K.M. Mueller T. Veepaschit J. Grimm C. Brehm K. Hrčková G. Lutz M.B. Ferreira H.B. Nono K.J. (2016b): Proteomic analysis of excretory-secretory products of Mesocestoides corti metacestodes reveals potential suppressors of dendritic cell functions. PLoS Negl. Trop. Dis. 10(10): e0005061. DOI: 10.1371/journal.pntd.0005061

  • Voehringer D. Shinkai K. Locksley R.m. (2004): Type 2 immunity reflects orchestrated recruitment of cells committed to IL-4 production. Immunity. 20(3): 267 – 277. DOI: 10.1016/S1074-7613(04)00026-3

  • Vuitton A. Gottstein B. (2010): Echinococcus multilocularis and its intermediate host: a model of parasite-host interplay. J. Biomed. Biotechnol. 2010: ID923193. DOI: 10.1155/2010/923193.

  • White T.R. Thompson R.C.A. Penhale W.J. (1982): A comparative study of the susceptibility of inbred-strains of mice to infection with Mesocestoides corti. Int. J. Parasitol. 12(1): 29 – 33. DOI: 10.1016/0020-7519(82)90091-1

  • Wyllie P.J. (1997): Apoptosis: An overview. Brit. Med. Bull. 53(3): 451 – 465. DOI: 10.1093/oxfordjournals.bmb.a011623

  • Zepeda N. Solano S. Copini N. Fernández A.M. Hernández L. Tato P. Molinari J.L. (2010): Decrease of peritoneal inflammatory CD4+ CD8+ CD19+ lymphocytes and apoptosis of eosinophils in a murine Taenia crassiceps infection. Parasitol. Res. 107(5): 1129 – 1135. DOI: 10.1007/s00436-010-1980-1

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