Factor H facilitates adherence of Neisseria gonorrhoeae to complement receptor 3 on eukaryotic cells.
Neisseria gonorrhoeae can engage human complement receptor 3 (CR3) directly or through surface-bound iC3b. Factor H (fH) that binds to bacteria facilitates conversion of C3b to iC3b. fH also binds directly to CR3 on professional phagocytes. Certain nonprofessional phagocytes, such as primary cervical epithelial cells, also express CR3. We hypothesized that fH could bridge bacteria to CR3 and facilitate gonococcal association with host cells. Specificity of the fH-CR3 interaction was confirmed using human CR3-transfected Chinese hamster ovary (CHO-CR3) cells. Using recombinant proteins that comprised contiguous fH domains (fH contains 20 short consensus repeat [SCR] domains) fused to murine Fc, we observed strong binding through SCRs 18-20, whereas weaker binding occurred through SCRs 6-10. Both regions also bound to unsialylated porin (Por) B.1A-expressing N. gonorrhoeae. Accordingly, fH-related protein 1 (three of its five SCRs are highly homologous to fH SCRs 18-20) bound to CHO-CR3 and to unsialylated PorB.1A gonococci. An alternatively spliced variant of fH called fH-like protein-1 (contains fH SCRs 1-7) bound to gonococci but minimally to CHO-CR3. An fH SCRs 6-20 construct enhanced binding of unsialylated PorB.1A gonococci to CHO-CR3. However, a construct that contained only the apparently relevant SCRs (6, 7, and 18-20) bound to CHO-CR3 and to gonococci separately, but did not enhance bacteria-CR3 interactions, suggesting that the intervening SCRs (8-17) may impart a configurational and spatial requirement for fH to bridge gonococci to CR3. These results indicate adherence between fH-coated gonococci and CR3 and may provide a means for gonococci to gain sanctuary into nonprofessional phagocytes.
Agarwal
Sarika
S
Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA. sarika.agarwal@umassmed.edu
Ram
Sanjay
S
Ngampasutadol
Jutamas
J
Gulati
Sunita
S
Zipfel
Peter F
PF
Rice
Peter A
PA
D000818:Animals; D016466:CHO Cells; D002469:Cell Separation; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D006801:Humans; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D014162:Transfection
D016177:Macrophage-1 Antigen; D017242:Complement Factor H
Sex Transm Dis. 1984 Apr-Jun;11(2):77-80
6431621
Eur J Immunol. 1987 Oct;17(10):1485-9
2445583
Annu Rev Cell Dev Biol. 2000;16:423-57
11031243
Mol Immunol. 2006 Jan;43(1-2):31-44
16011850
Fertil Steril. 2007 Oct;88(4 Suppl):1212-9
17562335
J Exp Med. 1998 Mar 2;187(5):743-52
9480984
Clin Microbiol Rev. 2004 Oct;17(4):965-81, table of contents
15489357
Infect Immun. 2002 Oct;70(10):5808-15
12228311
Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32
15870199
Microbes Infect. 2000 Mar;2(3):289-94
10758405
Infect Immun. 1978 Apr;20(1):267-72
78895
Mol Immunol. 2009 Sep;46(14):2808-17
19477524
Cell Tissue Res. 2001 Sep;305(3):285-98
11572082
Mol Immunol. 1999 Sep-Oct;36(13-14):809-18
10698334
J Immunol. 2007 Apr 1;178(7):4489-97
17372007
J Clin Invest. 1982 Oct;70(4):906-13
6288774
J Immunol. 2008 Aug 15;181(4):2610-9
18684951
Biochem Soc Trans. 2002 Nov;30(Pt 6):971-8
12440956
Infect Immun. 1983 May;40(2):816-9
6404835
J Biol Chem. 2001 Aug 24;276(34):32129-35
11406620
J Immunol. 2005 Nov 15;175(10):6465-72
16272300
J Immunol. 2010 Jan 15;184(2):912-21
20008295
Infect Immun. 2000 Sep;68(9):5354-63
10948165
Cell Microbiol. 2002 Sep;4(9):571-84
12390350
J Cell Biol. 1993 Feb;120(4):1031-43
7679388
Mol Microbiol. 2001 Nov;42(3):659-72
11722733
Infect Immun. 2009 May;77(5):2094-103
19273554
Biochem J. 1988 Jan 15;249(2):593-602
2963625
Int J Biochem. 1982;14(7):561-3
7106355
J Infect Dis. 1999 Jan;179(1):124-35
9841831
Cell Microbiol. 2001 Sep;3(9):611-22
11553013
Immunopharmacology. 1999 May;42(1-3):53-60
10408366
Biochem J. 1997 Sep 1;326 ( Pt 2):321-7
9291099
Exp Eye Res. 2007 Apr;84(4):635-45
17292886
Blood. 2009 Sep 17;114(12):2439-47
19528535
Infect Immun. 2005 Nov;73(11):7390-7
16239538
Trends Immunol. 2008 Aug;29(8):380-7
18602340
Methods Enzymol. 1994;236:137-47
7968606
Infect Immun. 1997 Mar;65(3):931-5
9038299
J Exp Med. 1988 Nov 1;168(5):1883-97
3141555
J Leukoc Biol. 1992 Feb;51(2):109-17
1358992
J Exp Med. 1998 Aug 17;188(4):671-80
9705949
J Immunol. 1995 Dec 15;155(12):5663-70
7499851
Semin Thromb Hemost. 2006 Mar;32(2):128-45
16575688
J Mol Biol. 2001 Jun 22;309(5):1117-38
11399083
J Infect Dis. 1985 Aug;152(2):339-43
3928769
J Immunol. 1998 Apr 15;160(8):4057-66
9558116
Mol Microbiol. 2000 Jan;35(1):32-43
10632875
J Infect Dis. 2007 Jul 1;196(1):124-33
17538892
Cell Microbiol. 2005 Aug;7(8):1197-211
16008586
Immunogenetics. 2004 May;56(2):77-82
15118848
Cell Microbiol. 2002 Sep;4(9):585-98
12390351
J Immunol. 2008 Mar 1;180(5):3426-35
18292569
J Biol Chem. 1993 Oct 15;268(29):22055-9
7691822
Infect Immun. 1981 Jun;32(3):985-94
6166568
Prog Clin Biol Res. 1995;392:49-58
8524957
Annu Rev Immunol. 2007;25:619-47
17201681
Immunol Today. 1999 Mar;20(3):135-40
10203705
Vaccine. 2008 Dec 30;26 Suppl 8:I9-14
19388158