title: Avirulent strains of Toxoplasma gondii infect macrophages by active invasion from the phagosome.
abstract: Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially used by avirulent strains of T. gondii and confers an infectious advantage over virulent strains for macrophage tropism.
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07101.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Marple
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.forename: David J
authors.initials: DJ
authors.lastname: Bzik
authors.forename: George S
authors.initials: GS
authors.lastname: Yap
mesh_terms: D000818:Animals; D002460:Cell Line; D008264:Macrophages / Q000469:parasitology* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010588:Phagosomes / Q000469:parasitology* / Q000473:pathology / Q000648:ultrastructure; D014122:Toxoplasma / Q000472:pathogenicity* / Q000648:ultrastructure; D014123:Toxoplasmosis / Q000469:parasitology / Q000473:pathology; D018523:Tropism; D014617:Vacuoles / Q000469:parasitology / Q000473:pathology / Q000648:ultrastructure
keywords: Trojan horse; apicomplexa; phagocytes; virulence
references.citation: Infect Immun. 2014 Jan;82(1):460-8
references.pmid: 24218483
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10514-10519
references.pmid: 16801557
references.citation: Cell Microbiol. 2006 Oct;8(10):1611-23
references.pmid: 16984416
references.citation: Infect Immun. 2011 Feb;79(2):756-66
references.pmid: 21098108
references.citation: Int J Parasitol. 2008 Jul;38(8-9):999-1006
references.pmid: 18191859
references.citation: J Immunol. 2009 Mar 15;182(6):3775-81
references.pmid: 19265156
references.citation: Nat Rev Immunol. 2011 Mar;11(3):187-200
references.pmid: 21350579
references.citation: J Biol Chem. 2011 Feb 4;286(5):3307-14
references.pmid: 21097503
references.citation: Proc Natl Acad Sci U S A. 2013 May 21;110(21):E1913-22
references.pmid: 23650399
references.citation: Nature. 1985 May 30-Jun 5;315(6018):416-9
references.pmid: 2860567
references.citation: J Cell Sci. 1995 Jun;108 ( Pt 6):2457-64
references.pmid: 7673360
references.citation: J Exp Med. 2011 Jan 17;208(1):195-212
references.pmid: 21199955
references.citation: Nature. 1992 Sep 3;359(6390):82-5
references.pmid: 1355855
references.citation: Science. 2003 Jan 17;299(5605):414-6
references.pmid: 12532022
references.citation: Infect Immun. 2009 Apr;77(4):1679-88
references.pmid: 19204091
references.citation: Cell. 1996 Mar 22;84(6):933-9
references.pmid: 8601316
references.citation: J Infect Dis. 2009 Apr 15;199(8):1155-67
references.pmid: 19265484
references.citation: Nature. 2002 Feb 21;415(6874):926-9
references.pmid: 11859373
references.citation: J Immunol. 2013 Nov 1;191(9):4818-27
references.pmid: 24078692
references.citation: Microbes Infect. 2011 Jan;13(1):96-102
references.pmid: 20951223
references.citation: Int J Parasitol. 2011 May;41(6):645-55
references.pmid: 21320505
references.citation: Exp Parasitol. 2013 Jun;134(2):160-4
references.pmid: 23538031
references.citation: J Parasitol. 2008 Feb;94(1):36-41
references.pmid: 18372619
references.citation: J Med Microbiol. 1996 Jun;44(6):418-24
references.pmid: 8636958
references.citation: J Immunol. 2004 Mar 15;172(6):3686-94
references.pmid: 15004172
references.citation: J Infect Dis. 1995 Dec;172(6):1561-6
references.pmid: 7594717
references.citation: Blood. 2006 Jan 1;107(1):309-16
references.pmid: 16051744
references.citation: Infect Immun. 2000 Aug;68(8):4822-6
references.pmid: 10899898
references.citation: Nat Methods. 2013 Feb;10(2):125-7
references.pmid: 23263690
references.citation: Exp Parasitol. 1999 Jun;92(2):87-99
references.pmid: 10366534
references.citation: Cell Host Microbe. 2013 Jan 16;13(1):42-53
references.pmid: 23290966
references.citation: PLoS Pathog. 2005 Nov;1(3):e24
references.pmid: 16304607
references.citation: J Exp Med. 2006 Sep 4;203(9):2063-71
references.pmid: 16940170
references.citation: J Exp Med. 1999 Dec 20;190(12):1783-92
references.pmid: 10601353
references.citation: Infect Immun. 2008 Jun;76(6):2671-7
references.pmid: 18390995
references.citation: Nat Rev Microbiol. 2012 Nov;10(11):766-78
references.pmid: 23070557
references.citation: mBio. 2013 Jul 09;4(4):
references.pmid: 23839215
references.citation: Cell Host Microbe. 2012 Oct 18;12(4):419-31
references.pmid: 23084912
references.citation: Cell Host Microbe. 2009 Mar 19;5(3):259-72
references.pmid: 19286135
references.citation: PLoS One. 2013 Nov 07;8(11):e80213
references.pmid: 24244652
references.citation: Science. 1990 Aug 10;249(4969):641-6
references.pmid: 2200126