title: Trypanosoma cruzi: Entry into Mammalian Host Cells and Parasitophorous Vacuole Formation.
abstract: Trypanosoma cruzi, the causative agent of Chagas disease, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are the metacyclic trypomastigotes, amastigotes, and bloodstream trypomastigotes. The recognition between the parasite and mammalian host cell, involves numerous molecules present in both cell types, and similar to several intracellular pathogens, T. cruzi is internalized by host cells via multiple endocytic pathways. Morphological studies demonstrated that after the interaction of the infective forms of T. cruzi with phagocytic or non-phagocytic cell types, plasma membrane (PM) protrusions can form, showing similarity with those observed during canonical phagocytosis or macropinocytic events. Additionally, several molecules known to be molecular markers of membrane rafts, macropinocytosis, and phagocytosis have been demonstrated to be present at the invasion site. These events may or may not depend on the host cell lysosomes and cytoskeleton. In addition, after penetration, components of the host endosomal-lysosomal system, such as early endosomes, late endosomes, and lysosomes, participate in the formation of the nascent parasitophorous vacuole (PV). Dynamin, a molecule involved in vesicle formation, has been shown to be involved in the PV release from the host cell PM. This review focuses on the multiple pathways that T. cruzi can use to enter the host cells until complete PV formation. We will describe different endocytic processes, such as phagocytosis, macropinocytosis, and endocytosis using membrane microdomains and clathrin-dependent endocytosis and show results that are consistent with their use by this smart parasite. We will also discuss others mechanisms that have been described, such as active penetration and the process that takes advantage of cell membrane wound repair.
authors.affiliation: Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil ; Laboratório de Biologia, Instituto Nacional de Metrologia, Qualidade e Tecnologia - Inmetro Duque de Caxias , Rio de Janeiro , Brazil.
authors.forename: Emile Santos
authors.initials: ES
authors.lastname: Barrias
authors.forename: Tecia Maria Ulisses
authors.initials: TM
authors.lastname: de Carvalho
authors.forename: Wanderley
authors.initials: W
authors.lastname: De Souza
keywords: Trypanosoma cruzi; active penetration; endocytosis; host cell; interaction; mammalian cell; phagocytosis
references.citation: Exp Parasitol. 1991 Jan;72(1):76-86
references.pmid: 1993466
references.citation: J Struct Biol. 2004 Sep;147(3):259-67
references.pmid: 15450295
references.citation: Annu Rev Biochem. 2010;79:803-33
references.pmid: 20196649
references.citation: J Exp Med. 1988 Aug 1;168(2):649-59
references.pmid: 3045248
references.citation: J Pathol. 2010 May;221(1):3-12
references.pmid: 20225336
references.citation: Traffic. 2000 Feb;1(2):100-6
references.pmid: 11208090
references.citation: J Immunol. 1991 Dec 15;147(12):4313-21
references.pmid: 1753102
references.citation: Parasitol Res. 2009 Jun;104(6):1251-60
references.pmid: 19283409
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466-70
references.pmid: 2138778
references.citation: J Cell Biol. 2011 Oct 3;195(1):7-17
references.pmid: 21969466
references.citation: Nat Rev Microbiol. 2006 Mar;4(3):229-36
references.pmid: 16489349
references.citation: Nat Cell Biol. 2006 Jan;8(1):46-54
references.pmid: 16341206
references.citation: Cell Struct Funct. 2002 Apr;27(2):91-8
references.pmid: 12207050
references.citation: Cell Struct Funct. 1995 Aug;20(4):275-84
references.pmid: 8521528
references.citation: Annu Rev Biochem. 2009;78:857-902
references.pmid: 19317650
references.citation: Curr Biol. 2007 Jul 3;17(13):1151-6
references.pmid: 17600709
references.citation: Annu Rev Cell Dev Biol. 2011;27:107-32
references.pmid: 21801009
references.citation: J Protozool. 1976 Nov;23(4):534-7
references.pmid: 826623
references.citation: Mem Inst Oswaldo Cruz. 1999;94 Suppl 1:149-52
references.pmid: 10677703
references.citation: Autophagy. 2009 Jan;5(1):6-18
references.pmid: 19115481
references.citation: Exp Parasitol. 1998 Sep;90(1):1-13
references.pmid: 9709024
references.citation: Subcell Biochem. 2008;47:101-9
references.pmid: 18512345
references.citation: Z Parasitenkd. 1982;68(1):7-14
references.pmid: 6753392
references.citation: Traffic. 2008 Aug;9(8):1299-315
references.pmid: 18445119
references.citation: Int J Parasitol. 2007 Nov;37(13):1431-41
references.pmid: 17582418
references.citation: Traffic. 2009 Apr;10(4):364-71
references.pmid: 19192253
references.citation: Nature. 1993 Aug 12;364(6438):639-42
references.pmid: 8350922
references.citation: Mol Biochem Parasitol. 1989 Jul;35(3):229-37
references.pmid: 2664507
references.citation: Cell Microbiol. 2009 Aug;11(8):1179-89
references.pmid: 19416270
references.citation: Br J Pharmacol. 2012 Mar;165(5):1333-47
references.pmid: 21797847
references.citation: Glycobiology. 2004 Jul;14(7):647-57
references.pmid: 15044384
references.citation: PLoS Negl Trop Dis. 2012;6(3):e1583
references.pmid: 22479662
references.citation: Mol Biochem Parasitol. 1985 Jun;16(1):85-96
references.pmid: 2412116
references.citation: Eur J Biochem. 1984 May 2;140(3):599-604
references.pmid: 6373254
references.citation: Nat Rev Immunol. 2010 May;10(5):353-64
references.pmid: 20395980
references.citation: J Exp Med. 2011 May 9;208(5):909-21
references.pmid: 21536739
references.citation: J Biol Chem. 1999 Jun 11;274(24):16754-9
references.pmid: 10358016
references.citation: PLoS Negl Trop Dis. 2011 Feb 01;5(2):e953
references.pmid: 21408103
references.citation: Infect Dis Clin North Am. 2012 Jun;26(2):275-91
references.pmid: 22632639
references.citation: Trends Cell Biol. 2010 Apr;20(4):177-86
references.pmid: 20153650
references.citation: Biochem Biophys Res Commun. 1994 Sep 15;203(2):967-71
references.pmid: 8093081
references.citation: Microbes Infect. 2012 Nov;14(14):1340-51
references.pmid: 23010292
references.citation: J Biol Chem. 2001 Jun 1;276(22):19382-9
references.pmid: 11278913
references.citation: Lancet. 2010 Apr 17;375(9723):1388-402
references.pmid: 20399979
references.citation: Parasitol Res. 2005 Jun;96(3):171-7
references.pmid: 15864650
references.citation: PLoS Biol. 2004 Sep;2(9):E261
references.pmid: 15328530
references.citation: Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1-13
references.pmid: 2700931
references.citation: Sci Rep. 2011;1:192
references.pmid: 22355707
references.citation: Immunity. 2005 May;22(5):539-50
references.pmid: 15894272
references.citation: J Immunol. 1994 Oct 1;153(7):3141-7
references.pmid: 8089492
references.citation: J Cell Biol. 1996 Jul;134(2):349-62
references.pmid: 8707821
references.citation: Curr Opin Cell Biol. 1998 Aug;10(4):504-12
references.pmid: 9719872
references.citation: J Exp Med. 1999 Dec 20;190(12):1849-56
references.pmid: 10601359
references.citation: Mol Biochem Parasitol. 1994 May;65(1):161-9
references.pmid: 7935622
references.citation: Histol Histopathol. 2010 Jan;25(1):99-112
references.pmid: 19924646
references.citation: Cell Mol Life Sci. 2012 Jun;69(11):1755-71
references.pmid: 22113372
references.citation: PLoS One. 2010 Jan 20;5(1):e7764
references.pmid: 20098746
references.citation: J Exp Med. 1994 Mar 1;179(3):1017-22
references.pmid: 8113670
references.citation: Cell Microbiol. 2011 Jul;13(7):943-54
references.pmid: 21501360
references.citation: FEBS Lett. 2000 Mar 31;470(3):305-8
references.pmid: 10745086
references.citation: Curr Opin Cell Biol. 2010 Aug;22(4):519-27
references.pmid: 20439156
references.citation: Parasitol Res. 1992;78(5):404-9
references.pmid: 1495918
references.citation: J Biol Chem. 1995 Oct 13;270(41):24146-9
references.pmid: 7592617
references.citation: Histochem Cell Biol. 2005 Jun;123(6):613-20
references.pmid: 15889267
references.citation: Cell Microbiol. 2004 Sep;6(9):829-38
references.pmid: 15272864
references.citation: Biochem Biophys Res Commun. 2002 Mar 1;291(3):516-21
references.pmid: 11855818
references.citation: Annu Rev Biochem. 2012;81:661-86
references.pmid: 22663081
references.citation: An Acad Bras Cienc. 2005 Mar;77(1):77-94
references.pmid: 15692679
references.citation: Immunol Cell Biol. 2011 Nov;89(8):836-43
references.pmid: 21423264
references.citation: Infect Immun. 1998 Sep;66(9):4331-9
references.pmid: 9712785
references.citation: Biochem Biophys Res Commun. 2009 Jan 16;378(3):478-82
references.pmid: 19032944
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):133-47
references.pmid: 15040446
references.citation: EMBO J. 2011 Aug 31;30(17):3481-500
references.pmid: 21878991
references.citation: Mem Inst Oswaldo Cruz. 1999;94 Suppl 1:143-7
references.pmid: 10677702
references.citation: BMC Cell Biol. 2008 Dec 17;9:68
references.pmid: 19087356
references.citation: Biochem Biophys Res Commun. 1984 Feb 29;119(1):228-35
references.pmid: 6322778
references.citation: Am J Physiol Cell Physiol. 2010 Nov;299(5):C876-81
references.pmid: 20739621
references.citation: Trends Microbiol. 1998 Oct;6(10):384-8
references.pmid: 9807780
references.citation: Subcell Biochem. 2008;47:58-69
references.pmid: 18512341
references.citation: Biochem Biophys Res Commun. 2007 Nov 23;363(3):828-34
references.pmid: 17904520
references.citation: Infect Immun. 1996 May;64(5):1770-7
references.pmid: 8613390
references.citation: Infect Immun. 2004 Nov;72(11):6717-21
references.pmid: 15501810
references.citation: Braz J Med Biol Res. 2000 Mar;33(3):269-78
references.pmid: 10719377
references.citation: J Exp Med. 1976 Jun 1;143(6):1402-20
references.pmid: 775012
references.citation: Infect Immun. 1989 Jun;57(6):1663-7
references.pmid: 2656520
references.citation: Int J Cell Biol. 2010;2010:
references.pmid: 20811486
references.citation: PLoS One. 2012;7(11):e47835
references.pmid: 23139754