The major objectives of this STD-CRC will be accomplished primarily through the study of two major STD pathogens C trachomatis and N. gonorrhoeae in the context of their natural settings - patients infected with these organisms. Six research projects and four service cores (Administrative, Clinical, Laboratory and Statistical) are proposed. In the first project (Jonathan Howland, PhD, PI), we propose to develop and evaluate an education intervention that will promote condom use among patients in our inner city public STD clinic; acquisition of chlamydial infection, in particular, will be a major outcome measure. In Project 2 (Joseph A. Hill, MD, PI and Deborah J. Anderson, PhD, Co-PI), we hypothesize that chronic sub-clinical chlamydial infection of the endometrium causes reproductive failure by stimulating local T-helper-I (TH1) cytokine mediated immune responses. We will characterize these events infertile women who fail in vitro fertilization (IVF) compared to IVF women who have a successful pregnancy. In Project 3 (You-Xun Zhang, PhD, PI), we will examine the role of chlamydial elongation factors Tu (EF-Tu) and Ts (EF-Ts), known to be regulators of cellular processes, in the persistence of latent chlamydial infection, and in influencing the differentiation of Chlamydia to form infectious elementary bodies. In addition to characterizing EF-Tu and EF-Ts in the laboratory, we will also track their activities in Chlamydia through analysis of their expressed m- RNAs under experimental and clinical conditions. In Project 4 (Douglas T. Golenbock, MD, PI), we will examine the immunostimulatory effects of chlamydial and gonococcal endotoxins and elucidate the chemical structures of Lipid A from Chlamydia and gonococci. We will also examine their abilities to interact with, and signal through, LPS receptors on phagocytes. In Project 5 (Michael A. Apicella, MD, PI), we will determine the mechanisms whereby gonococci gain access to the intracellular environment of target epithelial cells in the male genital tract, using wild type gonococci and a series of isogeneic lipooligosaccharide (LOS) mutants. We will also identify gonococcal genes which are expressed during infection of male urethral stratified squamous epithelial cells. In Project 6 (Lee M. Wetzler, MD, PI), to address the possibility of protective immunity in gonorrhea, we will employ an epidemiologically defined population of women who, when exposed to N. gonorrhoeae, either become infected or withstand it (75% overall become infected). We will examine whether women who resist infection are protected by virtue of their pre-existing immune status (both humoral and T-cell mediated).
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