Abstract
Amebic liver abscess (ALA) is a severe focal destruction of liver tissue caused by infection with the parasite Entamoeba histolytica (E. histolytica). In the past, tissue damage has been mainly attributed to pathogenicity factors of the parasite. However, the massive presence of innate immune cells raises the question whether host cells contribute to the destruction of the liver tissue as well. In this chapter, we discuss the role of neutrophils, monocytes, and macrophages during ALA in animal models for the disease. In brief, neutrophils contribute only partially to the observed pathology, whereas inflammatory monocytes and resident liver macrophages are substantially involved in tissue damage seen during E. histolytica infection. Therefore, we conclude beyond parasite-specific effector molecules, immune pathological mechanisms of the host substantially contribute to the development of ALA.
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References
Leippe M (1997) Amoebapores. Parasitol Today 13:178–183
Bruchhaus I, Loftus BJ, Hall N, Tannich E (2003) The intestinal protozoan parasite Entamoeba histolytica contains 20 cysteine protease genes, of which only a small subset is expressed during in vitro cultivation. Eukaryot Cell 2:501–509
Stanley SL Jr, Zhang T, Rubin D, Li E (1995) Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice. Infect Immun 63:1587–1590
Nowak N, Lotter H, Tannich E, Bruchhaus I (2004) Resistance of Entamoeba histolytica to the cysteine proteinase inhibitor E64 is associated with secretion of pro-enzymes and reduced pathogenicity. J Biol Chem 279:38260–38266
Hellberg A, Nickel R, Lotter H, Tannich E, Bruchhaus I (2001) Overexpression of cysteine proteinase 2 in Entamoeba histolytica or Entamoeba dispar increases amoeba-induced monolayer destruction in vitro but does not augment amoebic liver abscess formation in gerbils. Cell Microbiol 3:13–20
Tillack M, Nowak N, Lotter H, Bracha R, Mirelman D et al (2006) Increased expression of the major cysteine proteinases by stable episomal transfection underlines the important role of EhCP5 for the pathogenicity of Entamoeba histolytica. Mol Biochem Parasitol 149:58–64
Tillack M, Biller L, Irmer H, Freitas M, Gomes MA et al (2007) The Entamoeba histolytica genome: primary structure and expression of proteolytic enzymes. BMC Genomics 8:170
Davis PH, Chen M, Zhang X, Clark CG, Townsend RR et al (2009) Proteomic comparison of Entamoeba histolytica and Entamoeba dispar and the role of E. histolytica alcohol dehydrogenase 3 in virulence. PLoS Negl Trop Dis 3:e415
Clark CG, Alsmark UC, Tazreiter M, Saito-Nakano Y, Ali V et al (2007) Structure and content of the Entamoeba histolytica genome. Adv Parasitol 65:51–190
Blessmann J, Ali IK, Nu PA, Dinh BT, Viet TQ et al (2003) Longitudinal study of intestinal Entamoeba histolytica infections in asymptomatic adult carriers. J Clin Microbiol 41:4745–4750
Acuna-Soto R, Maguire JH, Wirth DF (2000) Gender distribution in asymptomatic and invasive amebiasis. Am J Gastroenterol 95:1277–1283
Ventura-Juárez J, Jarillo-Luna RA, Fuentes-Aguilar E, Pineda-Vázquez A, Munoz-Fernández L et al (2003) Human amoebic hepatic abscess: in situ interactions between trophozoites, macrophages, neutrophils and T cells. Parasite Immunol 25:503–511
Shibayama M, Campos-Rodriguez R, Ramirez-Rosales A, Martinez-Palomo A, Tsutsumi V (1997) Morphological analysis of amebic liver abscess produced by intraperitoneal inoculation of Entamoeba histolytica trophozoites in hamsters. Arch Med Res 28:207–210
Tsutsumi V, Mena-Lopez R, Anaya-Velazquez F, Martinez-Palomo A (1984) Cellular bases of experimental amebic liver abscess formation. Am J Pathol 117:81–91
Chadee K, Meerovitch E (1984) The pathogenesis of experimentally induced amebic liver abscess in the gerbil (Meriones unguiculatus). Am J Pathol 117:71–80
Cieslak PR, Virgin HWT, Stanley SL Jr (1992) A severe combined immunodeficient (SCID) mouse model for infection with Entamoeba histolytica. J Exp Med 176:1605–1609
Biller L, Schmidt H, Krause E, Gelhaus C, Matthiesen J et al (2009) Comparison of two genetically related Entamoeba histolytica cell lines derived from the same isolate with different pathogenic properties. Proteomics 9:4107–4120
Lotter H, Jacobs T, Gaworski I, Tannich E (2006) Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease. Infect Immun 74:118–124
Matthiesen J, Bar AK, Bartels AK, Marien D, Ofori S et al (2013) Overexpression of specific cysteine peptidases confers pathogenicity to a nonpathogenic Entamoeba histolytica clone. MBio. doi:10.1128/mBio.00072-13
Cohn ZA, Hirsch JG (1960) The influence of phagocytosis on the intracellular distribution of granule-associated components of polymorphonuclear leucocytes. J Exp Med 112:1015–1022
Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223
Guerrant RL, Brush J, Ravdin JI, Sullivan JA, Mandell GL (1981) Interaction between Entamoeba histolytica and human polymorphonuclear neutrophils. J Infect Dis 143:83–93
Denis M, Chadee K (1989) Human neutrophils activated by interferon-gamma and tumour necrosis factor-alpha kill Entamoeba histolytica trophozoites in vitro. J Leukoc Biol 46:270–274
Mainardi CL, Dixit SN, Kang AH (1980) Degradation of type IV (basement membrane) collagen by a proteinase isolated from human polymorphonuclear leukocyte granules. J Biol Chem 255:5435–5441
Mainardi CL, Hasty DL, Seyer JM, Kang AH (1980) Specific cleavage of human type III collagen by human polymorphonuclear leukocyte elastase. J Biol Chem 255:12006–12010
Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10:427–439
Salata RA, Ravdin JI (1986) The interaction of human neutrophils and Entamoeba histolytica increases cytopathogenicity for liver cell monolayers. J Infect Dis 154:19–26
Shi C, Hohl TM, Leiner I, Equinda MJ, Fan X et al (2011) Ly6G+ neutrophils are dispensable for defense against systemic Listeria monocytogenes infection. J Immunol 187:5293–5298
Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11:762–774
Seydel KB, Zhang T, Stanley SL Jr (1997) Neutrophils play a critical role in early resistance to amebic liver abscesses in severe combined immunodeficient mice. Infect Immun 65:3951–3953
Vollmar B, Menger MD (2009) The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev 89:1269–1339
Bilzer M, Roggel F, Gerbes AL (2006) Role of Kupffer cells in host defense and liver disease. Liver Int 26:1175–1186
Kolios G, Valatas V, Kouroumalis E (2006) Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol 12:7413–7420
Kinoshita M, Uchida T, Sato A, Nakashima M, Nakashima H et al (2010) Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. J Hepatol 53:903–910
Lin HH, Faunce DE, Stacey M, Terajewicz A, Nakamura T et al (2005) The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 201:1615–1625
Sanchez-Madrid F, Simon P, Thompson S, Springer TA (1983) Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1. J Exp Med 158:586–602
Smith MJ, Koch GL (1987) Differential expression of murine macrophage surface glycoprotein antigens in intracellular membranes. J Cell Sci 87(Pt 1):113–119
Roberts RA, Ganey PE, Ju C, Kamendulis LM, Rusyn I et al (2007) Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol Sci 96:2–15
Nakashima H, Kinoshita M, Nakashima M, Habu Y, Shono S et al (2008) Superoxide produced by Kupffer cells is an essential effector in concanavalin A-induced hepatitis in mice. Hepatology 48:1979–1988
Yang R, Zou X, Koskinen ML, Tenhunen J (2012) Ethyl pyruvate reduces liver injury at early phase but impairs regeneration at late phase in acetaminophen overdose. Crit Care 16:R9
Ghadirian E, Meerovitch E, Hartmann DP (1980) Protection against amebic liver abscess in hamsters by means of immunization with amebic antigen and some of its fractions. Am J Trop Med Hyg 29:779–784
Denis M, Chadee K (1989) Cytokine activation of murine macrophages for in vitro killing of Entamoeba histolytica trophozoites. Infect Immun 57:1750–1756
Ghadirian E, Denis M (1992) In vivo activation of macrophages by IFN-gamma to kill Entamoeba histolytica trophozoites in vitro. Parasite Immunol 14:397–404
Ghadirian E, Salimi A (1993) In vitro effect of recombinant interferon gamma in combination with LPS on amoebicidal activity of murine Kupffer cells. Immunobiology 188:203–219
Denis M, Ghadirian E (1992) Activated mouse macrophages kill Entamoeba histolytica trophozoites by releasing reactive nitrogen intermediates. Microb Pathog 12:193–198
Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7:311–317
Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA (1998) Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480–483
Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82
Serbina NV, Jia T, Hohl TM, Pamer EG (2008) Monocyte-mediated defense against microbial pathogens. Annu Rev Immunol 26:421–452
Bosschaerts T, Guilliams M, Stijlemans B, Morias Y, Engel D et al (2010) Tip-DC development during parasitic infection is regulated by IL-10 and requires CCL2/CCR2, IFN-gamma and MyD88 signaling. PLoS Pathog 6:e1001045
Aldridge JR Jr, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C et al (2009) TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci USA 106:5306–5311
Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7:77–86
Karlmark KR, Wasmuth HE, Trautwein C, Tacke F (2008) Chemokine-directed immune cell infiltration in acute and chronic liver disease. Expert Rev Gastroenterol Hepatol 2:233–242
Baeck C, Wehr A, Karlmark KR, Heymann F, Vucur M et al (2012) Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut 61:416–426
Helk E, Bernin H, Ernst T, Ittrich H, Jacobs T et al (2013) TNF-alpha-mediated liver destruction by Kupffer cells and Ly6Chi monocytes during Entamoeba histolytica infection. PLoS Pathog 9:e1003096
Dunay IR, Damatta RA, Fux B, Presti R, Greco S et al (2008) Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity 29:306–317
Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756
Aggarwal BB, Gupta SC, Kim JH (2012) Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 119:651–665
Quintanar-Quintanar ME, Jarillo-Luna A, Rivera-Aguilar V, Ventura-Juarez J, Tsutsumi V et al (2004) Immunosuppressive treatment inhibits the development of amebic liver abscesses in hamsters. Med Sci Monit 10:BR317–BR324
Acknowledgments
The research presented in this chapter was supported by grants from the Deutsche Forschungsgemeinschaft SFB 841 (“Liver inflammation: Infection, Immune Regulation and Consequences”). E.H. is supported by studentships from the SFB 841, Hamburg, Germany. H.B. is supported by the Werner-Otto Stiftung, Hamburg, Germany. H.L. is supported by and holds a group leadership in the Department of Molecular Parasitology from the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. We thank Claudia Marggraff for the excellent immunohistology of ALA.
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Helk, E., Bernin, H., Lotter, H. (2015). Host Immunity and Tissue Destruction During Liver Abscess Formation. In: Nozaki, T., Bhattacharya, A. (eds) Amebiasis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55200-0_26
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