title: Protective immunity against mouse upper genital tract pathology correlates with high IFNγ but low IL-17 T cell and anti-secretion protein antibody responses induced by replicating chlamydial organisms in the airway.
abstract: To search for optimal immunization conditions for inducing protective immunity against upper genital tract pathologies caused by chlamydial intravaginal infection, we compared protection efficacy in mice immunized intranasally or intramuscularly with live or inactivated Chlamydia muridarum organisms. Mice immunized intranasally with live organisms developed strong protection against both vaginal shedding of infectious organisms and upper genital tract pathologies. The protection correlated with a robust antigen-specific T cell response with high IFNγ but low IL-17. Although a significant level of IL-5 was also detected, these mice maintained an overall Th1-dorminant immunity following immunization and challenge infection. On the contrary, mice immunized intranasally with inactivated organisms or intramuscularly with live or inactivated organisms produced high levels of IL-17 and still developed significant upper genital tract pathologies. High titers of antibodies against chlamydial secretion antigens were detected only in mice immunized intranasally with live organisms but not mice in other groups, suggesting that the intranasally inoculated live organisms were able to undergo replication and immune responses to the chlamydial secretion proteins may contribute to protective immunity. These observations have provided important information on how to develop subunit vaccines for inducing protective immunity against urogenital infection with Chlamydia trachomatis organisms.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Chunxue
authors.initials: C
authors.lastname: Lu
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057138:Bacterial Shedding; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology / Q000517:prevention & control*; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D051379:Mice; D060737:Reproductive Tract Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D020381:Interleukin-17; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D007371:Interferon-gamma
references.citation: J Immunol. 2010 Mar 1;184(5):2602-10
references.pmid: 20124098
references.citation: Infect Immun. 2000 Dec;68(12):6979-87
references.pmid: 11083822
references.citation: Infect Immun. 2004 Dec;72(12):7164-71
references.pmid: 15557641
references.citation: Infect Immun. 2005 Dec;73(12):8153-60
references.pmid: 16299310
references.citation: Chin Med J (Engl). 1999 Oct;112(10):938-41
references.pmid: 11717981
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1160-5
references.pmid: 11158611
references.citation: Infect Immun. 1996 Dec;64(12):5341-8
references.pmid: 8945586
references.citation: Infect Immun. 2006 Oct;74(10):5513-21
references.pmid: 16988226
references.citation: J Immunol. 2010 Aug 1;185(3):1670-80
references.pmid: 20581152
references.citation: Infect Immun. 2007 Feb;75(2):666-76
references.pmid: 17118987
references.citation: Mol Microbiol. 2009 Jun;72(6):1423-37
references.pmid: 19460098
references.citation: Expert Rev Vaccines. 2009 Oct;8(10):1365-77
references.pmid: 19803759
references.citation: Infect Immun. 2004 Jan;72(1):451-60
references.pmid: 14688126
references.citation: J Exp Med. 2001 Apr 16;193(8):935-42
references.pmid: 11304554
references.citation: Infect Immun. 2000 Jan;68(1):192-6
references.pmid: 10603387
references.citation: PLoS Pathog. 2010 Nov 04;6(11):e1001179
references.pmid: 21079691
references.citation: Am J Ophthalmol. 1979 Mar;87(3):350-3
references.pmid: 434096
references.citation: Infect Immun. 1996 Nov;64(11):4830-3
references.pmid: 8890246
references.citation: Infect Immun. 1999 Mar;67(3):1379-85
references.pmid: 10024585
references.citation: J Exp Med. 1988 Mar 1;167(3):817-31
references.pmid: 2450954
references.citation: J Infect Dis. 1989 Jun;159(6):1105-10
references.pmid: 2656878
references.citation: Infect Immun. 1999 Apr;67(4):1606-13
references.pmid: 10084993
references.citation: J Infect Dis. 2010 Aug 15;202(3):427-35
references.pmid: 20575661
references.citation: J Immunol. 2009 Nov 1;183(9):5886-95
references.pmid: 19812198
references.citation: Infect Immun. 1995 Dec;63(12):4704-14
references.pmid: 7591126
references.citation: Infect Immun. 2001 Jul;69(7):4667-72
references.pmid: 11402013
references.citation: J Immunol. 2011 Mar 15;186(6):3615-21
references.pmid: 21296978
references.citation: Nucleic Acids Res. 2000 Mar 15;28(6):1397-406
references.pmid: 10684935
references.citation: J Immunol. 1993 Oct 1;151(7):3728-36
references.pmid: 7690812
references.citation: Sex Transm Dis. 1990 Jul-Sep;17(3):115-21
references.pmid: 2247800
references.citation: Trends Microbiol. 2009 Oct;17(10):467-74
references.pmid: 19765998
references.citation: J Bacteriol. 2011 May;193(10):2498-509
references.pmid: 21441519
references.citation: Cell Immunol. 2006 Aug;242(2):110-7
references.pmid: 17116296
references.citation: Mol Microbiol. 1995 Feb;15(4):617-26
references.pmid: 7783634
references.citation: Infect Immun. 2002 Jun;70(6):2741-51
references.pmid: 12010958
references.citation: Infect Immun. 1998 Nov;66(11):5457-61
references.pmid: 9784557
references.citation: Microbes Infect. 2002 Mar;4(3):333-40
references.pmid: 11909744
references.citation: Infect Immun. 1991 Apr;59(4):1465-9
references.pmid: 2004824
references.citation: J Exp Med. 1998 Feb 16;187(4):487-96
references.pmid: 9463399
references.citation: Infect Immun. 2008 Feb;76(2):515-22
references.pmid: 18025098
references.citation: Trends Microbiol. 2003 Jan;11(1):44-51
references.pmid: 12526854
references.citation: Indian J Med Res. 1968 Aug;56(8):1289-94
references.pmid: 5711608
references.citation: Microbiology (Reading). 2011 Apr;157(Pt 4):1134-1144
references.pmid: 21233161
references.citation: Infect Immun. 1995 Dec;63(12):4661-8
references.pmid: 7591120
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):9947-8
references.pmid: 15226494
references.citation: Infect Immun. 1999 Apr;67(4):1763-9
references.pmid: 10085016
references.citation: Infect Immun. 2006 Dec;74(12):6722-9
references.pmid: 17015458
references.citation: Infect Immun. 2008 Aug;76(8):3415-28
references.pmid: 18474640
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10166-71
references.pmid: 15199184
references.citation: Infect Immun. 2005 Mar;73(3):1568-77
references.pmid: 15731055
references.citation: Sex Transm Dis. 2005 Jan;32(1):49-56
references.pmid: 15614121
references.citation: J Hyg Epidemiol Microbiol Immunol. 1957;1(2):109-20
references.pmid: 13502539
references.citation: Vaccine. 2007 Jan 4;25(2):283-90
references.pmid: 16949182
references.citation: Infect Immun. 2006 Mar;74(3):1490-9
references.pmid: 16495519
references.citation: Curr Pharm Des. 2010;16(33):3656-60
references.pmid: 21128900
references.citation: Curr Opin Microbiol. 2008 Feb;11(1):53-9
references.pmid: 18299248
references.citation: Arch Environ Health. 1964 Apr;8:518-26
references.pmid: 14107660
references.citation: Infect Immun. 1992 Sep;60(9):3714-8
references.pmid: 1500180
references.citation: Am J Ophthalmol. 1967 May;63(5):Suppl:1615-30
references.pmid: 4960884
references.citation: Infect Immun. 2009 Nov;77(11):5059-70
references.pmid: 19737908
references.citation: Infect Immun. 1990 Oct;58(10):3438-41
references.pmid: 1698181
references.citation: Infect Immun. 2008 Jun;76(6):2746-57
references.pmid: 18391011
references.citation: Hum Reprod. 2002 Aug;17(8):2073-8
references.pmid: 12151439
references.citation: PLoS One. 2010 May 21;5(5):e10768
references.pmid: 20505822
references.citation: J Immunol. 2009 Jul 15;183(2):1291-300
references.pmid: 19542374
references.citation: J Clin Invest. 2011 Feb;121(2):554-68
references.pmid: 21206087
references.citation: Infect Immun. 2008 Mar;76(3):942-51
references.pmid: 18086816
references.citation: Infect Immun. 1994 May;62(5):1576-83
references.pmid: 7513303
references.citation: J Immunol. 2005 Dec 1;175(11):7536-42
references.pmid: 16301662
references.citation: J Exp Med. 1997 Nov 17;186(10):1623-31
references.pmid: 9362523
references.citation: Am J Ophthalmol. 1967 May;63(5):Suppl:1443-54
references.pmid: 6025170
references.citation: J Immunol. 2005 Feb 1;174(3):1701-8
references.pmid: 15661934
references.citation: J Gastroenterol Hepatol. 2010 Apr;25(4):750-7
references.pmid: 20492330
references.citation: Front Microbiol. 2010 Oct 19;1:114
references.pmid: 21738522
references.citation: Infect Immun. 2011 Mar;79(3):1349-62
references.pmid: 21149587
references.citation: J Exp Med. 1990 Jul 1;172(1):203-12
references.pmid: 1694217
references.citation: Cell Immunol. 2004 Jul;230(1):56-64
references.pmid: 15541719