Complement receptor 3 promotes severe ross river virus-induced disease.
Alphaviruses such as Ross River virus (RRV) and chikungunya virus are mosquito-transmitted viruses that cause explosive epidemics of debilitating arthritis and myositis affecting millions of humans worldwide. Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b(-/-)), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. CR3 deficiency had no effect on viral replication, nor did it diminish the magnitude, kinetics, and composition of the cellular infiltrates at the sites of inflammation. However, the genetic absence of CR3 diminished the expression of specific proinflammatory and cytotoxic effectors, including S100A9/S100A8 and interleukin-6, within the inflamed tissues, suggesting that CR3-dependent signaling at the sites of inflammation contributes to tissue damage and severe disease.
Morrison
Thomas E
TE
The Carolina Vaccine Institute, University of North Carolina at Chapel Hill, 9024 Burnett Womack, CB #7292, Manning Drive, Chapel Hill, NC 27599. heisem@med.unc.edu.
Simmons
Jason D
JD
Heise
Mark T
MT
D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D040502:Calgranulin B / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007596:Joints / Q000473:pathology / Q000821:virology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology / Q000821:virology; D012398:Ross River virus / Q000276:immunology*; D012720:Severity of Illness Index; D019562:Viral Load
D040502:Calgranulin B; D015850:Interleukin-6; D016177:Macrophage-1 Antigen
Lancet Infect Dis. 2008 Jan;8(1):2-3
18156079
Cardiovasc Res. 2003 Sep 1;59(3):723-33
14499874
J Cell Biol. 1990 Dec;111(6 Pt 2):3129-39
1980124
J Clin Invest. 1989 Jun;83(6):2008-17
2566624
Arthritis Res Ther. 2006;8(3):R69
16613612
J Immunol. 2006 Aug 1;177(3):1661-9
16849475
J Exp Med. 1987 Mar 1;165(3):733-49
3102677
Med J Aust. 2002 Oct 7;177(7):352-5
12358576
Immunity. 2006 Aug;25(2):271-83
16872848
J Infect Dis. 2008 Jun 1;197(11):1585-93
18433328
Nature. 1987 Nov 5-11;330(6143):80-2
3313057
Microbes Infect. 2000 Mar;2(3):289-94
10758405
Lancet. 2007 Dec 1;370(9602):1840-6
18061059
Immunity. 2002 Feb;16(2):157-68
11869678
Eur J Immunol. 2005 Sep;35(9):2691-8
16094691
Proc Natl Acad Sci U S A. 1983 Sep;80(18):5699-703
6225125
Nat Rev Immunol. 2005 Aug;5(8):641-54
16056256
J Exp Med. 1982 Oct 1;156(4):1000-9
7153706
Virology. 1983 Aug;129(1):170-87
6310876
J Clin Invest. 1996 Jul 1;98(1):50-61
8690804
J Immunol. 2005 Mar 15;174(6):3668-75
15749905
PLoS One. 2007 Jun 13;2(6):e527
17565380
J Clin Invest. 2007 Nov;117(11):3224-35
17932565
J Immunol. 2006 Aug 1;177(3):1904-12
16849503
Am J Pathol. 2003 Sep;163(3):947-56
12937135
Lancet Infect Dis. 2007 May;7(5):319-27
17448935
Emerg Infect Dis. 2008 May;14(5):852-4
18439383
Aust N Z J Med. 1985 Jun;15(3):336-9
2998316
J Virol. 2007 May;81(10):5132-43
17314163
Nat Rev Immunol. 2003 Jan;3(1):23-35
12511873
J Immunol. 2002 Jul 1;169(1):454-9
12077276
Biochem Biophys Res Commun. 1995 Feb 6;207(1):168-74
7857261
J Immunol. 1999 Jun 15;162(12):7285-93
10358177
J Biochem. 1997 Sep;122(3):595-600
9348089
J Immunol. 2004 Oct 15;173(8):4775-8
15470016
Clin Microbiol Rev. 2001 Oct;14(4):909-32, table of contents
11585790
J Immunol. 2007 Jan 15;178(2):1086-95
17202372
J Immunol. 1999 Feb 15;162(4):2281-90
9973505
Immunity. 2002 Apr;16(4):547-58
11970878
J Clin Invest. 1996 Jan 1;97(1):244-9
8550842
Crit Rev Immunol. 2000;20(3):197-222
10968371
J Immunol. 1985 May;134(5):3307-15
2984286
J Immunol. 1995 Nov 15;155(10):4861-7
7594489
Aust N Z J Med. 1981 Apr;11(2):168-73
6944041
J Exp Med. 1983 Jul 1;158(1):258-63
6864163
Trans R Soc Trop Med Hyg. 1965 Mar;59:186-97
14297194
J Virol. 2006 Jan;80(2):737-49
16378976
Lancet Infect Dis. 2007 May;7(5):306-7
17448932
J Immunol. 2001 Mar 1;166(5):3377-83
11207294
J Virol. 2000 Oct;74(19):9294-9
10982376
J Immunol. 1996 Feb 1;156(3):1235-46
8558003
PLoS Pathog. 2008 Mar 14;4(3):e1000023
18369473
Nat Immunol. 2004 Oct;5(10):981-6
15454921
Proc Natl Acad Sci U S A. 1988 Oct;85(20):7734-8
2971974
Arthritis Rheum. 2000 Feb;43(2):365-9
10693876
Clin Exp Immunol. 1988 Jun;72(3):510-5
3048809
J Infect Dis. 2000 Jan;181(1):27-34
10608747
J Gen Virol. 2007 Sep;88(Pt 9):2363-2377
17698645
J Immunol. 2001 Jan 1;166(1):574-81
11123339
Curr Opin Rheumatol. 2004 Jul;16(4):374-9
15201600