Differences in human macrophage receptor usage, lysosomal fusion kinetics and survival between logarithmic and metacyclic Leishmania infantum chagasi promastigotes.
The obligate intracellular protozoan, Leishmania infantum chagasi (Lic) undergoes receptor-mediated phagocytosis by macrophages followed by a transient delay in phagolysosome maturation. We found differences in the pathway through which virulent Lic metacyclic promastigotes or avirulent logarithmic promastigotes are phagocytosed by human monocyte-derived macrophages (MDMs). Both logarithmic and metacyclic promastigotes entered MDMs through a compartment lined by the third complement receptor (CR3). In contrast, many logarithmic promastigotes entered through vacuoles lined by mannose receptors (MR) whereas most metacyclic promastigotes did not (P < 0.005). CR3-positive vacuoles containing metacyclic promastigotes stained for caveolin-1 protein, suggesting CR3 localizes in caveolae during phagocytosis. Following entry, the kinetics of phagolysosomal maturation and intracellular survival also differed. Vacuoles containing metacyclic parasites did not accumulate lysosome-associated membrane protein-1 (LAMP-1) at early times after phagocytosis, whereas vacuoles with logarithmic promastigotes did. MDMs phagocytosed greater numbers of logarithmic than metacyclic promastigotes, yet metacyclics ultimately replicated intracellularly with greater efficiency. These data suggest that virulent metacyclic Leishmania promastigotes fail to ligate macrophage MR, and enter through a path that ultimately enhances intracellular survival. The relatively quiescent entry of virulent Leishmania spp. into macrophages may be accounted for by the ability of metacyclic promastigotes to selectively bypass deleterious entry pathways.
Ueno
Norikiyo
N
Department of Microbiology, the University of Iowa, Iowa City, IA, USA.
Bratt
Carol L
CL
Rodriguez
Nilda E
NE
Wilson
Mary E
ME
D000818:Animals; D002402:Cathepsin D / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism / Q000469:parasitology; D051242:Caveolin 1 / Q000378:metabolism; D018929:Cell Culture Techniques; D006790:Host-Parasite Interactions; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D018314:Leishmania infantum / Q000472:pathogenicity / Q000502:physiology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism* / Q000469:parasitology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014774:Virulence
D051242:Caveolin 1; D037181:Lectins, C-Type; D052118:Lysosomal-Associated Membrane Protein 1; D016177:Macrophage-1 Antigen; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D002402:Cathepsin D
J Immunol. 2001 Jun 15;166(12):7477-85
11390501
J Exp Med. 1988 Jul 1;168(1):279-92
3294332
Microbes Infect. 2001 Jul;3(9):755-61
11489424
Exp Parasitol. 2008 Jan;118(1):129-33
17706646
J Leukoc Biol. 2006 Sep;80(3):563-71
16816147
Science. 1984 Mar 30;223(4643):1417-9
6701528
Exp Parasitol. 2001 Oct;99(2):97-103
11748963
J Biol Chem. 2000 Oct 27;275(43):33883-9
10931831
J Exp Med. 2005 Oct 3;202(7):987-99
16203868
Cell Microbiol. 2006 Jul;8(7):1106-20
16819964
J Immunol. 1985 Oct;135(4):2785-9
3161950
Res Immunol. 1998 Sep-Oct;149(7-8):689-92
9851525
Gac Med Mex. 2008 Mar-Apr;144(2):99-104
18590029
Transfusion. 2006 Dec;46(12):2083-9
17176319
J Exp Med. 1987 Jan 1;165(1):140-5
3025330
Cell Microbiol. 2005 Sep;7(9):1263-70
16098214
Adv Exp Med Biol. 2000;479:1-14
10897405
Adv Parasitol. 1992;31:175-254
1496927
J Immunol. 1986 Jun 15;136(12):4681-8
3711662
J Immunol. 1995 Sep 15;155(6):3102-11
7673725
Infect Immun. 2007 Feb;75(2):1017-24
17118986
Exp Parasitol. 1987 Oct;64(2):147-56
3653336
Nature. 1987 May 28-Jun 3;327(6120):329-31
3035377
Methods Mol Biol. 2007;412:273-87
18453118
Nat Med. 2005 Jun;11(6):653-60
15880118
J Parasitol. 1991 Jun;77(3):411-6
2040953
Infect Agents Dis. 1992 Aug;1(4):200-6
1365546
Cell Microbiol. 2000 Oct;2(5):365-77
11207592
J Invest Dermatol. 2008 Sep;128(9):2225-31
18337829
Science. 1992 Jun 26;256(5065):1812-5
1615326
Trends Cell Biol. 1995 May;5(5):183-6
14731444
Nat Cell Biol. 2001 May;3(5):473-83
11331875
Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):9155-9
8090785
Mol Biochem Parasitol. 2008 Feb;157(2):148-59
18067978
Infect Immun. 1985 Aug;49(2):305-11
3160661
J Immunol. 1990 Dec 15;145(12):4311-6
2147941
Annu Rev Immunol. 1999;17:593-623
10358769
J Immunol. 1989 Jul 15;143(2):617-22
2525590
J Med Entomol. 2000 Jan;37(1):134-40
15218917
Cell Microbiol. 2000 Apr;2(2):115-26
11207568
Thromb Haemost. 2007 Sep;98(3):488-96
17849036
J Exp Med. 1983 Dec 1;158(6):2016-23
6227677
J Exp Med. 1985 Jul 1;162(1):324-31
3891904
Infect Immun. 1988 Feb;56(2):363-9
2962944
Trends Immunol. 2002 Mar;23(3):158-64
11864845
Eur J Biochem. 1987 Apr 1;164(1):213-21
3549304
J Leukoc Biol. 1994 Feb;55(2):161-8
8301212
J Parasitol. 1976 Jun;62(3):360-5
778371
Mol Biochem Parasitol. 2002 Mar;120(1):33-40
11849703
Microbes Infect. 2000 Mar;2(3):279-88
10758404
Crit Rev Immunol. 2004;24(3):179-92
15482253
Int J Parasitol. 2002 Oct;32(11):1371-7
12350372
J Leukoc Biol. 2007 May;81(5):1188-96
17261547
Am J Trop Med Hyg. 1985 May;34(3):456-9
4039899
J Cell Sci. 1999 Sep;112 Pt 18:2993-3002
10462516
J Leukoc Biol. 2003 Feb;73(2):209-12
12554797