title: IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa.
abstract: 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.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Walsh
authors.forename: Terra A
authors.initials: TA
authors.lastname: Cederroth
authors.forename: Akinobu
authors.initials: A
authors.lastname: Kamei
authors.forename: Yamara S
authors.initials: YS
authors.lastname: Coutinho-Sledge
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: 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
chemical_list: D000907:Antibodies, Bacterial; D020381:Interleukin-17; D008070:Lipopolysaccharides; D019081:O Antigens; D054406:Pseudomonas Vaccines; D014613:Vaccines, Attenuated
references.citation: Infect Immun. 2000 Jul;68(7):3998-4004
references.pmid: 10858214
references.citation: Infect Immun. 2005 Sep;73(9):5782-8
references.pmid: 16113296
references.citation: Mol Microbiol. 2000 Sep;37(5):981-8
references.pmid: 10972817
references.citation: J Infect Dis. 2001 Feb 1;183(3):444-52
references.pmid: 11133376
references.citation: Science. 2001 Mar 23;291(5512):2413-7
references.pmid: 11264538
references.citation: Infect Immun. 2001 Jul;69(7):4521-7
references.pmid: 11401995
references.citation: J Exp Med. 2001 Aug 20;194(4):519-27
references.pmid: 11514607
references.citation: Am J Respir Cell Mol Biol. 2001 Sep;25(3):335-40
references.pmid: 11588011
references.citation: J Leukoc Biol. 2002 Jan;71(1):1-8
references.pmid: 11781375
references.citation: J Bacteriol. 2002 Feb;184(4):952-61
references.pmid: 11807055
references.citation: Infect Immun. 2002 Mar;70(3):1507-17
references.pmid: 11854239
references.citation: FEMS Microbiol Lett. 2002 May 7;210(2):277-83
references.pmid: 12044687
references.citation: Am J Respir Cell Mol Biol. 2003 Jan;28(1):9-11
references.pmid: 12495927
references.citation: Am J Respir Cell Mol Biol. 2003 Jan;28(1):42-50
references.pmid: 12495931
references.citation: J Immunol. 2003 Feb 15;170(4):1958-63
references.pmid: 12574364
references.citation: Infect Immun. 2003 Mar;71(3):1453-61
references.pmid: 12595463
references.citation: J Immunol. 2003 May 1;170(9):4432-6
references.pmid: 12707317
references.citation: Crit Care Med. 2005 Oct;33(10):2184-93
references.pmid: 16215368
references.citation: Nat Immunol. 2005 Nov;6(11):1123-32
references.pmid: 16200070
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: Infect Immun. 2006 Apr;74(4):2187-95
references.pmid: 16552049
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: J Immunol. 2006 Jul 1;177(1):566-73
references.pmid: 16785554
references.citation: Eur J Immunol. 2006 Nov;36(11):2857-67
references.pmid: 17048275
references.citation: J Immunol. 2006 Dec 1;177(11):7980-9
references.pmid: 17114471
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L519-28
references.pmid: 17071720
references.citation: Nat Med. 2007 Feb;13(2):139-45
references.pmid: 17290272
references.citation: Annu Rev Immunol. 2007;25:821-52
references.pmid: 17201677
references.citation: J Exp Med. 2007 May 14;204(5):995-1001
references.pmid: 17470641
references.citation: Clin Vaccine Immunol. 2008 Feb;15(2):367-75
references.pmid: 18094113
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2530-5
references.pmid: 14983043
references.citation: Infect Immun. 2004 Jul;72(7):4224-32
references.pmid: 15213167
references.citation: Clin Exp Immunol. 2004 Sep;137(3):478-85
references.pmid: 15320896
references.citation: J Mol Biol. 1969 May 14;41(3):459-72
references.pmid: 4896022
references.citation: J Immunol. 1983 Nov;131(5):2178-83
references.pmid: 6195255
references.citation: J Exp Med. 1984 Nov 1;160(5):1338-49
references.pmid: 6208308
references.citation: J Immunol. 1991 Jan 1;146(1):316-20
references.pmid: 1898604
references.citation: Gene. 1991 Jan 2;97(1):109-21
references.pmid: 1899844
references.citation: Gene. 1991 Jul 15;103(1):87-92
references.pmid: 1908810
references.citation: Med Microbiol Immunol. 1991;180(3):135-41
references.pmid: 1833615
references.citation: Clin Exp Immunol. 1995 Jan;99(1):98-105
references.pmid: 7813116
references.citation: Immunology. 1994 Nov;83(3):362-9
references.pmid: 7835960
references.citation: Infect Immun. 1995 Sep;63(9):3497-501
references.pmid: 7642283
references.citation: Arthritis Rheum. 2004 Feb;50(2):650-9
references.pmid: 14872510
references.citation: Adv Exp Med Biol. 1995;371B:755-9
references.pmid: 7502892
references.citation: Infect Immun. 1996 Jun;64(6):2288-94
references.pmid: 8675339
references.citation: J Infect Dis. 1996 Sep;174(3):537-43
references.pmid: 8769611
references.citation: Crit Care Med. 1997 Nov;25(11):1862-7
references.pmid: 9366771
references.citation: APMIS. 1997 Nov;105(11):838-42
references.pmid: 9393554
references.citation: J Clin Invest. 1998 Jun 1;101(11):2598-605
references.pmid: 9616231
references.citation: Infect Immun. 1998 Aug;66(8):3719-26
references.pmid: 9673254
references.citation: Int Immunopharmacol. 2005 Mar;5(3):591-9
references.pmid: 15683854
references.citation: J Clin Invest. 2005 May;115(5):1281-9
references.pmid: 15841217
references.citation: J Immunol. 2005 Jul 1;175(1):404-12
references.pmid: 15972674
references.citation: Clin Exp Immunol. 2000 Aug;121(2):275-82
references.pmid: 10931142