Abstract
Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes.
Highlights
Female genital tract (FGT) infections, including common sexually transmitted infections (STI), seriously compromise the health of women
Several chemokine receptors and integrin genes were significantly up-regulated in infected animals compared to the control group and the four most significant genes were selected for further validation: Ccr5, Itgax, Cxcr6 and Ccr2 (Fig 1)
While CD4+ T cells only had a significant increase in the percentage of CD44+ activated TEM cells (S1e Fig), CD8+ T cells demonstrated a significant increase in both, CD44+ and CD44- subsets after infection (S1e and S1f Fig)
Summary
Female genital tract (FGT) infections, including common sexually transmitted infections (STI), seriously compromise the health of women. Effective vaccines exist for human papilloma virus and hepatitis B virus, efforts to develop vaccines against herpes simplex virus type 2 (HSV-2), HIV and bacterial STI have been hampered by an inability to effectively measure immune responses in the genital tract. Such vaccines need to be able to generate robust immune responses at site of potential exposure in order to provide rapid control of primary infection [3, 4]. Current assays used to understand the magnitude and quality of immune responses in the FGT rely primarily on blood samples and provide an incomplete picture of localized immune control
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