ORIGINAL ARTICLE: Two Different Homing Pathways Involving Integrin β7 and E‐selectin Significantly Influence Trafficking of CD4 Cells to the Genital Tract Following <i>Chlamydia muridarum</i> Infection

Kelly, Kathleen A.; Chan, Ann M.; Butch, Anthony W.; Darville, Toni

doi:10.1111/j.1600-0897.2009.00704.x

Cited by 24 publications

(25 citation statements)

References 30 publications

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“…However, inflammatory cytokines can also activate bystander T cells at the site of infection independently of antigen specificity (26). Previous work characterizing integrin receptors required for T cell recruitment to the genital mucosa focused exclusively on memory CD4 + T cell lines (23), polyclonal CD4 + T cells (24), or bulk CD4 + T cells (25) but never examined naïve C. trachomatis -specific CD4 + T cells. However, only by using naïve antigen-specific T cells is it possible to properly model primary infection.…”

Section: Resultsmentioning

confidence: 99%

Integrin α4β1 Is Necessary for CD4+ T Cell–Mediated Protection against Genital Chlamydia trachomatis Infection

Davila

Olive

Starnbach

2014

The Journal of Immunology

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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 interferon-gamma (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. Here 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.

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Section: Resultsmentioning

confidence: 99%

Integrin α4β1 Is Necessary for CD4+ T Cell–Mediated Protection against Genital Chlamydia trachomatis Infection

Davila

Olive

Starnbach

2014

The Journal of Immunology

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“…This is particularly important because due to the compartmentalization of the mucosal immune system, stimulation of the various mucosal inductive sites results in an uneven distribution of immune responses at the various effector sites [39, 47, 48]. Overall, the most effective way to induce an immune response at a specific effector site is to locally administer the immunization, or perhaps, stimulate sites with related lymph drainage [39, 49, 50]. …”

Section: Discussionmentioning

confidence: 99%

Enhancement of the protective efficacy of a Chlamydia trachomatis recombinant vaccine by combining systemic and mucosal routes for immunization

Ralli-Jain

Tifrea

Cheng

et al. 2010

Vaccine

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Chlamydia trachomatis causes respiratory and sexually transmitted infections. Here, we tested a vaccine formulated with the recombinant major outer membrane protein from C. trachomatis mouse pneumonitis (CT-MoPn) for its ability to protect mice against an intranasal (i.n.) challenge. The adjuvants CpG and Montanide were used for systemic routes, intramuscular (i.m.) and subcutaneous (s.c.), and cholera toxin for mucosal routes, sublingual (s.l.) and colonic (c.l.). Mucosal immunizations were performed either alone or in combination with systemic routes. Mice inoculated i.n. with 104 inclusion-forming units (IFU) of CT-MoPn served as a positive control and the Neisseria gonorrhoeae recombinant porin B (Ng-rPorB) as the negative antigen control. Immunized animals were challenged i.n. with 104 IFU of CT-MoPn. Following immunization the combination groups showed high chlamydial serum IgG titers (s.l.+i.m.+s.c. 25,600; c.l+i.m.+s.c. 102,400) and the IgG2a/IgG1 ratios indicated a Th1 response. Following the i.n. challenge the s.l./i.m.+s.c. group showed the best protection as demonstrated by an increase in body weight of 0.3% over the 10 day course of infection. A statistically significant difference was found when compared with the Ng-rPorB immunized animals that had lost 20% of their original body weight (P < 0.05). In addition, the repeated measures ANOVA test showed significant difference in body weight change for the combined immunized groups versus their mucosal counterparts and also the systemic immunized group. A statistically significant difference (P < 0.05) was also observed in the median number of IFUs recovered from the lungs when the s.l.+i.m.+s.c. (2.8 × 106 ) and c.l.+i.m.+s.c. (3.4 × 106) groups where compared to their respective mucosal only groups (s.l.: 61.9 × 106 and c.l: 136.2 × 106) and the control Ng-rPorB immunized mice (198.2 × 106) (P < 0.05). In conclusion, a combined systemic plus mucosal vaccination provides better protection against a respiratory challenge with C. trachomatis than either systemic or mucosal immunizations alone.

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“…Once naive T cells are primed in a lymph node, a global switch of their homing program occurs, which enables them, while trafficking through the blood circulation, to detect chemokines and adhesion molecules which direct them to their tissue destination. Furthermore, T cell homing to the genital mucosa involves either ␣1␤1, ␣4␤1 (201), or ␣4␤7/E selectin (202) in Chlamydia-infected mice. Both systemic and mucosal immunization routes have been shown to be able to induce both antibodyand cell-mediated immune responses in the genital tract, with intranasal immunization often being more effective (203,204).…”

Section: Vaccination Routesmentioning

confidence: 99%

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

Vasilevsky¹,

Greub

Nardelli-Haefliger

et al. 2014

Clin Microbiol Rev

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SUMMARY Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and despite significant advances in chlamydial research, a prophylactic vaccine has yet to be developed. This Gram-negative obligate intracellular bacterium, which often causes asymptomatic infection, may cause pelvic inflammatory disease (PID), ectopic pregnancies, scarring of the fallopian tubes, miscarriage, and infertility when left untreated. In the genital tract, Chlamydia trachomatis infects primarily epithelial cells and requires Th1 immunity for optimal clearance. This review first focuses on the immune cells important in a chlamydial infection. Second, we summarize the research and challenges associated with developing a chlamydial vaccine that elicits a protective Th1-mediated immune response without inducing adverse immunopathologies.

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ORIGINAL ARTICLE: Two Different Homing Pathways Involving Integrin β7 and E‐selectin Significantly Influence Trafficking of CD4 Cells to the Genital Tract Following Chlamydia muridarum Infection

Cited by 24 publications

References 30 publications

Integrin α4β1 Is Necessary for CD4+ T Cell–Mediated Protection against Genital Chlamydia trachomatis Infection

Integrin α4β1 Is Necessary for CD4+ T Cell–Mediated Protection against Genital Chlamydia trachomatis Infection

Enhancement of the protective efficacy of a Chlamydia trachomatis recombinant vaccine by combining systemic and mucosal routes for immunization

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

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