title: Integrin α4β1 is necessary for CD4+ T cell-mediated protection against genital Chlamydia trachomatis infection.
abstract: Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection in the United States and a significant health burden worldwide. Protection from Chlamydia infection in the genital mucosa is dependent on IFN-γ derived from CD4(+) Th1 cells. These CD4(+) T cells must home successfully to the genital tract to exert their effector function and decrease C. trachomatis burden. Although adhesion receptors expressed by CD4(+) T cells in the genital tract have been characterized, the integrin receptor required for Chlamydia-specific CD4(+) T cell-mediated protection has not been explored. In this study, we demonstrate that C. trachomatis infection of the upper genital tract results in recruitment of Chlamydia-specific CD4(+) T cells robustly expressing the integrin α4β1. Interfering with α4β1, but not α4β7, function resulted in defective CD4(+) T cell trafficking to the uterus and high bacterial load. We conclude that integrin α4β1 is necessary for CD4(+) T cell-mediated protection against C. trachomatis infection in the genital mucosa. By identifying homing molecules required for successful CD4(+) T cell trafficking to C. trachomatis-infected tissues, we will be better equipped to design vaccines that elicit sterilizing, long-lasting immunity without inducing immune pathologies in the upper genital tract.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors.forename: Sergio J
authors.initials: SJ
authors.lastname: Davila
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Olive
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005836:Genitalia, Female / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D039041:Integrin alpha4beta1 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D039041:Integrin alpha4beta1