The class A scavenger receptor, macrophage receptor with collagenous structure, is the major phagocytic receptor for Clostridium sordellii expressed by human decidual macrophages.
Clostridium sordellii is an emerging pathogen associated with highly lethal female reproductive tract infections following childbirth, abortion, or cervical instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii infections present major challenges to the development of better preventive and therapeutic strategies against this problem. We sought to determine the mechanisms whereby uterine decidual macrophages phagocytose this bacterium and tested the hypothesis that human decidual macrophages use class A scavenger receptors to internalize unopsonized C. sordellii. In vitro phagocytosis assays with human decidual macrophages incubated with pharmacological inhibitors of class A scavenger receptors (fucoidan, polyinosinic acid, and dextran sulfate) revealed a role for these receptors in C. sordellii phagocytosis. Soluble macrophage receptor with collagenous structure (MARCO) receptor prevented C. sordellii internalization, suggesting that MARCO is an important class A scavenger receptor in decidual macrophage phagocytosis of this microbe. Peritoneal macrophages from MARCO-deficient mice, but not wild-type or scavenger receptor AI/II-deficient mice, showed impaired C. sordellii phagocytosis. MARCO-null mice were more susceptible to death from C. sordellii uterine infection than wild-type mice and exhibited impaired clearance of this bacterium from the infected uterus. Thus, MARCO is an important phagocytic receptor used by human and mouse macrophages to clear C. sordellii from the infected uterus.
Thelen
Tennille
T
Molecular, Cellular, and Developmental Biology Graduate Program, Eastern Michigan University, Ypsilanti, MI 48197, USA.
Hao
Yibai
Y
Medeiros
Alexandra I
AI
Curtis
Jeffrey L
JL
Serezani
Carlos H
CH
Kobzik
Lester
L
Harris
Lisa H
LH
Aronoff
David M
DM
D000293:Adolescent; D000328:Adult; D000818:Animals; D003015:Clostridium Infections / Q000276:immunology*; D047989:Paraclostridium sordellii / Q000276:immunology; D003656:Decidua / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
C490460:MARCO protein, human; D011971:Receptors, Immunologic
J Exp Med. 2004 Jul 19;200(2):267-72
15263032
Ann Med. 2004;36(5):347-54
15478309
J Immunol. 1990 Jan 1;144(1):263-70
2104888
J Immunol. 2005 Nov 1;175(9):6058-64
16237101
N Engl J Med. 2000 May 18;342(20):1500-7
10816189
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1863-7
8127896
Clin Infect Dis. 2002 Dec 1;35(11):1441-3
12439811
J Immunol Methods. 1990 Sep 14;132(2):181-9
2145368
Microbiology (Reading). 2003 Jun;149(Pt 6):1377-1386
12777479
J Innate Immun. 2009;1(2):153-63
20375573
J Immunol. 2007 May 1;178(9):5912-20
17442975
Cell Microbiol. 2009 Aug;11(8):1160-9
19388903
J Cell Biol. 2005 Aug 1;170(3):477-85
16061696
Hum Reprod. 2005 Apr;20(4):1057-66
15746201
Proc Natl Acad Sci U S A. 1990 Dec;87(23):9133-7
2251254
Placenta. 1990 Nov-Dec;11(6):467-75
2290798
Anaerobe. 2010 Apr;16(2):155-60
19527792
PLoS One. 2008 Apr 30;3(4):e2078
18446208
Microbes Infect. 2001 Feb;3(2):149-59
11251301
Reprod Sci. 2010 Mar;17(3):209-18
20065301
Infect Immun. 2009 Jan;77(1):85-97
18852237
Lancet Infect Dis. 2009 Dec;9(12):725-6
19926032
Atherosclerosis. 2005 Sep;182(1):1-15
15904923
J Immunol. 2008 Nov 15;181(10):7147-56
18981136
J Exp Med. 1999 May 3;189(9):1497-506
10224290
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4356-64
17003426
J Biol Chem. 2002 Sep 6;277(36):33378-85
12097327
Am J Respir Cell Mol Biol. 2006 Jun;34(6):766-74
16474098
J Control Release. 2001 Sep 11;76(1-2):59-71
11532313
Mol Immunol. 2008 Jun;45(11):3278-88
18423602
Am J Physiol. 1995 Dec;269(6 Pt 1):L721-6
8572233
J Immunol. 1996 Dec 15;157(12):5221-4
8955165
Reproduction. 2005 May;129(5):631-7
15855626
Expert Rev Mol Med. 2006 Nov 22;8(28):1-25
17118220
Am J Obstet Gynecol. 2009 Nov;201(5):459.e1-7
19628200
Infect Immun. 2004 Sep;72(9):5204-15
15322015
J Immunol. 2008 Jun 15;180(12):8222-30
18523288
N Engl J Med. 2005 Dec 1;353(22):2352-60
16319384
Am J Reprod Immunol. 2004 Feb;51(2):117-22
14748837
Science. 2004 May 14;304(5673):1014-8
15143282
Infect Immun. 1996 Aug;64(8):3318-25
8757870
J Immunol. 2004 Jul 1;173(1):559-65
15210817
Anaerobe. 2010 Apr;16(2):125-30
19559804
Infect Immun. 1997 May;65(5):1916-25
9125580
J Immunol. 2005 Dec 15;175(12):8032-41
16339540
Blood. 2009 Jan 22;113(4):887-92
18849484
J Biol Chem. 2006 Apr 28;281(17):11834-45
16407294
Eur J Immunol. 2008 Nov;38(11):3068-79
18924218
Clin Infect Dis. 2006 Dec 1;43(11):1436-46
17083018
Nature. 1997 Mar 20;386(6622):292-6
9069289
Mol Immunol. 2010 Jul;47(11-12):1989-96
20471681