Integrin α4β1 is necessary for CD4+ T cell-mediated protection against genital Chlamydia trachomatis infection

J Immunol. 2014 May 1;192(9):4284-93. doi: 10.4049/jimmunol.1303238. Epub 2014 Mar 21.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Chemotaxis, Leukocyte / immunology
  • Chlamydia Infections / immunology*
  • Chlamydia trachomatis / immunology*
  • Female
  • Flow Cytometry
  • Genitalia, Female / immunology
  • Genitalia, Female / metabolism
  • Genitalia, Female / microbiology
  • Integrin alpha4beta1 / immunology*
  • Integrin alpha4beta1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism
  • Polymerase Chain Reaction

Substances

  • Integrin alpha4beta1