IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa.
In a murine model of acute fatal pneumonia, we previously showed that nasal immunization with a live-attenuated aroA deletant of Pseudomonas aeruginosa strain PAO1 elicited LPS serogroup-specific protection, indicating that opsonic Ab to the LPS O Ag was the most important immune effector. Because P. aeruginosa strain PA14 possesses additional virulence factors, we hypothesized that a live-attenuated vaccine based on PA14 might elicit a broader array of immune effectors. Thus, an aroA deletant of PA14, denoted PA14DeltaaroA, was constructed. PA14DeltaaroA-immunized mice were protected against lethal pneumonia caused not only by the parental strain but also by cytotoxic variants of the O Ag-heterologous P. aeruginosa strains PAO1 and PAO6a,d. Remarkably, serum from PA14DeltaaroA-immunized mice had very low levels of opsonic activity against strain PAO1 and could not passively transfer protection, suggesting that an antibody-independent mechanism was needed for the observed cross-serogroup protection. Compared with control mice, PA14DeltaaroA-immunized mice had more rapid recruitment of neutrophils to the airways early after challenge. T cells isolated from P. aeruginosa DeltaaroA-immunized mice proliferated and produced IL-17 in high quantities after coculture with gentamicin-killed P. aeruginosa. Six hours following challenge, PA14DeltaaroA-immunized mice had significantly higher levels of IL-17 in bronchoalveolar lavage fluid compared with unimmunized, Escherichia coli-immunized, or PAO1DeltaaroA-immunized mice. Antibody-mediated depletion of IL-17 before challenge or absence of the IL-17 receptor abrogated the PA14DeltaaroA vaccine's protection against lethal pneumonia. These data show that IL-17 plays a critical role in antibody-independent vaccine-induced protection against LPS-heterologous strains of P. aeruginosa in the lung.
Priebe
Gregory P
GP
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Walsh
Rebecca L
RL
Cederroth
Terra A
TA
Kamei
Akinobu
A
Coutinho-Sledge
Yamara S
YS
Goldberg
Joanna B
JB
Pier
Gerald B
GB
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002478:Cells, Cultured; D005260:Female; D020381:Interleukin-17 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000145:classification / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019081:O Antigens / Q000145:classification / Q000235:genetics / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D054406:Pseudomonas Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D012703:Serotyping; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D020381:Interleukin-17; D008070:Lipopolysaccharides; D019081:O Antigens; D054406:Pseudomonas Vaccines; D014613:Vaccines, Attenuated
Infect Immun. 2000 Jul;68(7):3998-4004
10858214
Infect Immun. 2005 Sep;73(9):5782-8
16113296
Mol Microbiol. 2000 Sep;37(5):981-8
10972817
J Infect Dis. 2001 Feb 1;183(3):444-52
11133376
Science. 2001 Mar 23;291(5512):2413-7
11264538
Infect Immun. 2001 Jul;69(7):4521-7
11401995
J Exp Med. 2001 Aug 20;194(4):519-27
11514607
Am J Respir Cell Mol Biol. 2001 Sep;25(3):335-40
11588011
J Leukoc Biol. 2002 Jan;71(1):1-8
11781375
J Bacteriol. 2002 Feb;184(4):952-61
11807055
Infect Immun. 2002 Mar;70(3):1507-17
11854239
FEMS Microbiol Lett. 2002 May 7;210(2):277-83
12044687
Am J Respir Cell Mol Biol. 2003 Jan;28(1):9-11
12495927
Am J Respir Cell Mol Biol. 2003 Jan;28(1):42-50
12495931
J Immunol. 2003 Feb 15;170(4):1958-63
12574364
Infect Immun. 2003 Mar;71(3):1453-61
12595463
J Immunol. 2003 May 1;170(9):4432-6
12707317
Crit Care Med. 2005 Oct;33(10):2184-93
16215368
Nat Immunol. 2005 Nov;6(11):1123-32
16200070
Immunity. 2006 Feb;24(2):179-89
16473830
Infect Immun. 2006 Apr;74(4):2187-95
16552049
Nature. 2006 May 11;441(7090):231-4
16648837
J Immunol. 2006 Jul 1;177(1):566-73
16785554
Eur J Immunol. 2006 Nov;36(11):2857-67
17048275
J Immunol. 2006 Dec 1;177(11):7980-9
17114471
Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L519-28
17071720
Nat Med. 2007 Feb;13(2):139-45
17290272
Annu Rev Immunol. 2007;25:821-52
17201677
J Exp Med. 2007 May 14;204(5):995-1001
17470641
Clin Vaccine Immunol. 2008 Feb;15(2):367-75
18094113
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2530-5
14983043
Infect Immun. 2004 Jul;72(7):4224-32
15213167
Clin Exp Immunol. 2004 Sep;137(3):478-85
15320896
J Mol Biol. 1969 May 14;41(3):459-72
4896022
J Immunol. 1983 Nov;131(5):2178-83
6195255
J Exp Med. 1984 Nov 1;160(5):1338-49
6208308
J Immunol. 1991 Jan 1;146(1):316-20
1898604
Gene. 1991 Jan 2;97(1):109-21
1899844
Gene. 1991 Jul 15;103(1):87-92
1908810
Med Microbiol Immunol. 1991;180(3):135-41
1833615
Clin Exp Immunol. 1995 Jan;99(1):98-105
7813116
Immunology. 1994 Nov;83(3):362-9
7835960
Infect Immun. 1995 Sep;63(9):3497-501
7642283
Arthritis Rheum. 2004 Feb;50(2):650-9
14872510
Adv Exp Med Biol. 1995;371B:755-9
7502892
Infect Immun. 1996 Jun;64(6):2288-94
8675339
J Infect Dis. 1996 Sep;174(3):537-43
8769611
Crit Care Med. 1997 Nov;25(11):1862-7
9366771
APMIS. 1997 Nov;105(11):838-42
9393554
J Clin Invest. 1998 Jun 1;101(11):2598-605
9616231
Infect Immun. 1998 Aug;66(8):3719-26
9673254
Int Immunopharmacol. 2005 Mar;5(3):591-9
15683854
J Clin Invest. 2005 May;115(5):1281-9
15841217
J Immunol. 2005 Jul 1;175(1):404-12
15972674
Clin Exp Immunol. 2000 Aug;121(2):275-82
10931142