title: The roles of complement receptor 3 and Fcγ receptors during Leishmania phagosome maturation.
abstract: Leishmania are intracellular parasites adapted to surviving in macrophages, whose primary function is elimination of invading pathogens. Leishmania entry into host cells is receptor-mediated. These parasites are able to engage multiple host cell-surface receptors, including MR, TLRs, CR3, and FcγRs. Here, we investigated the role of CR3 and FcγR engagement on the maturation of Leishmania-containing phagosomes using CD11b-/- and FcγR-/- macrophages, and assessing EEA1 and lysosome-associated proteins is necessary for the phagosome maturation delay, characteristic of Leishmania infection. Leishmania-containing phagosomes do not fuse with lyosomes until 5 h postinfection in WT mice. Phagolysosome fusion occurs by 1 h in CD11b and FcγR common chain KO macrophages, although receptor deficiency does not influence Leishmania entry or viability. We also investigated the influence of serum components and their effects on phagosome maturation progression. Opsonization with normal mouse serum, complement-deficient serum, or serum from Leishmania-infected mice all influenced phagosome maturation progression. Our results indicate that opsonophagocytosis influences phagosomal trafficking of Leishmania without altering the intracellular fate.
authors.affiliation: Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Polando
authors.forename: Upasna Gaur
authors.initials: UG
authors.lastname: Dixit
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Carter
authors.forename: Blake
authors.initials: B
authors.lastname: Jones
authors.forename: James P
authors.initials: JP
authors.lastname: Whitcomb
authors.forename: Wibke
authors.initials: W
authors.lastname: Ballhorn
authors.forename: Melissa
authors.initials: M
authors.lastname: Harintho
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Jerde
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: McDowell
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007891:Leishmania / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010588:Phagosomes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D016177:Macrophage-1 Antigen; D017452:Receptors, IgG
keywords: CD11b; EEA1; LAMP1; deficient; mannose receptor
references.citation: Immunol Res. 2002;25(3):219-27
references.pmid: 12018461
references.citation: Nat Immunol. 2000 Nov;1(5):441-6
references.pmid: 11062505
references.citation: Mol Cell Biol. 2000 May;20(10):3685-94
references.pmid: 10779358
references.citation: Crit Rev Microbiol. 2002;28(3):187-248
references.pmid: 12385499
references.citation: J Biol Chem. 1977 Jun 25;252(12):4305-12
references.pmid: 301140
references.citation: J Exp Med. 1997 Jun 16;185(12):2061-8
references.pmid: 9182677
references.citation: Eur J Immunol. 2004 Jan;34(1):184-93
references.pmid: 14971044
references.citation: J Immunol. 2005 May 15;174(10):6340-5
references.pmid: 15879134
references.citation: Infect Immun. 2008 Feb;76(2):623-31
references.pmid: 18070890
references.citation: J Exp Med. 2006 Jan 23;203(1):177-88
references.pmid: 16418399
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000628
references.pmid: 19834555
references.citation: Infect Immun. 1999 Sep;67(9):4477-84
references.pmid: 10456889
references.citation: Eur J Immunol. 2000 Sep;30(9):2729-40
references.pmid: 11009109
references.citation: J Immunol. 1995 Sep 15;155(6):3102-11
references.pmid: 7673725
references.citation: PLoS Pathog. 2009 Apr;5(4):e1000381
references.pmid: 19381261
references.citation: Cell Microbiol. 2005 Nov;7(11):1647-58
references.pmid: 16207251
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8609-13
references.pmid: 8378337
references.citation: J Exp Med. 1999 Jan 4;189(1):25-35
references.pmid: 9874561
references.citation: J Immunol. 1990 Jun 15;144(12):4817-24
references.pmid: 1972169
references.citation: Cell Microbiol. 1999 Jul;1(1):19-32
references.pmid: 11207538
references.citation: Parasite Immunol. 2001 May;23(5):259-65
references.pmid: 11309136
references.citation: J Immunol. 2001 Jan 15;166(2):1141-7
references.pmid: 11145695
references.citation: Blood. 1999 Jun 15;93(12):4387-94
references.pmid: 10361137
references.citation: Science. 1995 Sep 29;269(5232):1869-72
references.pmid: 7569927
references.citation: J Leukoc Biol. 2006 Oct;80(4):774-86
references.pmid: 16857732
references.citation: J Immunol. 1991 Apr 15;146(8):2747-53
references.pmid: 1707920
references.citation: Exp Parasitol. 2001 Oct;99(2):97-103
references.pmid: 11748963
references.citation: Annu Rev Immunol. 2000;18:393-422
references.pmid: 10837064
references.citation: Infect Immun. 1996 Jun;64(6):2206-15
references.pmid: 8675328
references.citation: Infect Immun. 2006 May;74(5):2613-8
references.pmid: 16622197
references.citation: J Leukoc Biol. 1996 Jun;59(6):883-90
references.pmid: 8691074
references.citation: BMC Pharmacol. 2001;1:1
references.pmid: 11299045
references.citation: Infect Immun. 2001 Dec;69(12):7729-35
references.pmid: 11705954
references.citation: Mol Biochem Parasitol. 1988 Apr;28(3):285-93
references.pmid: 3386685
references.citation: J Immunol. 1989 Jul 15;143(2):617-22
references.pmid: 2525590
references.citation: Microb Pathog. 2003 Sep;35(3):125-31
references.pmid: 12927520
references.citation: Microbes Infect. 2009 Feb;11(2):215-22
references.pmid: 19070677
references.citation: J Immunol. 1991 Sep 15;147(6):1983-94
references.pmid: 1679838
references.citation: J Exp Med. 1985 Jul 1;162(1):324-31
references.pmid: 3891904
references.citation: Microbes Infect. 2003 Oct;5(12):1064-9
references.pmid: 14554247
references.citation: Trends Parasitol. 2001 Nov;17(11):545-51
references.pmid: 11872400
references.citation: Infect Immun. 1988 Feb;56(2):363-9
references.pmid: 2962944
references.citation: Eur J Biochem. 1987 Apr 1;164(1):213-21
references.pmid: 3549304
references.citation: Blood. 2010 Dec 9;116(24):5170-80
references.pmid: 20829368
references.citation: Parasitology. 1998 Apr;116 ( Pt 4):305-9
references.pmid: 9585932
references.citation: Microbes Infect. 2002 Jul;4(9):975-81
references.pmid: 12106791
references.citation: Annu Rev Immunol. 2001;19:275-90
references.pmid: 11244038
references.citation: Semin Cell Biol. 1993 Oct;4(5):315-22
references.pmid: 8257783