CHEMOKINE REGULATION OF MUCOSAL IMMUNITY AGAINST GENITAL CHLAMYDIAL INFECTION

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Genital infection by the obligate intracellular bacterium, Chlamydia trachomatis, is the most common bacterial sexually transmitted disease (STD) in the United States, with four million annual cases that cost $2.18 billion. In women the infection can lead to serious complications, including pelvic inflammatory disease, ectopic pregnancy and infertility. Many of the infections are asymptomatic and irreversible complications may be the first symptoms. The obvious concern that Chlamydia poses a potential threat to human reproduction, well-being and national budgets has intensified research on intervention and prevention strategies, of which a vaccine is a high priority. Anti-chlamydial vaccine research include the use of animal models for studying the pathogenesis and immunobiology of the disease, and defining antigens and immune effectors mediating immunity. These studies have shown that T cell- mediated immune responses, involving the induction and recruitment of T helper type 1 (Th1) cells into the genital mucosa is crucial for chlamydial immunity. Such factors would likely influence the genital mucosal expression and regulation of chemokines released by injected epithelial cells, chemokine receptors on recruited leukocytes, adhesion molecules involved in genital mucosal lymphoepithelial interactions, and local cytokine secretion. The focus of this proposal is to use novel in vitro and in vivo models of chlamydial infection and molecular and biochemical techniques to investigate the recruitment and maintenance of immune effectors in the genital mucosa following an infection. Specific studies will: (a) identify the chemokines elaborated by infected epithelial cells, for recruiting Th1 cells into the genital tract; and (b) identify certain adhesion molecules that are up-regulated after chlamydial infection and play a role in the retention of effectors in the genital tract. The results from this study will contribute to a better understanding of the regulatory mechanisms of effector recruitment and retention in the genital mucosa during chlamydial infection, which may lead to the designing of rational strategies to enhance the efficacy and long-term protective immunity of a chlamydial vaccine.