Over four million men and women suffer from chlamydial genital infection annually. Women bear a special burden because of their increased risk of adverse reproductive consequences. C. trachomatis is responsible for 25-50% of the estimated one million cases of pelvic inflammatory disease/year. The mechanism of the disease process is not understood. Our goal is to elucidate the basic biology of chlamydial growth in human epithelial cells in order to learn how persistent infection is accomplished since the majority of cases of tubal disease associated with chlamydial salpingitis appear to result from chronic, subclinical infection. We shall grow primary human endometrial epithelial cells in a polarized orientation to determine if infectious chlamydiae: (i) enter and release progeny at the apical surface but transport antigens to the basolateral surface for interaction with the immune system -monitored by transmission and immunoelectron microscopy (TEM and IEM) and (ii) exploit the receptor-mediated endocytic pathway for entry by localizing clathrin in chlamydia- containing coated pits and transferrin in chlamydia-containing endosomes. Clathrin will be detected by IEM using post- embedding staining on Lowicryl sections with second affinity gold-labeled antibody amplification. TEM and subcellular fractionation followed by the density-shift technique will be used to determine if chlamydiae localize initially in the transferrin - containing endosomes. Horseradish peroxidase covalently bound to transferrin is used to place peroxidase in the endosome. Peroxidase catalized polymerization of diaminobenzidine within the vesicles causes either a black precipitate on stained thin sections or an increase in bouyant density, allowing endosomes to be separated by density gradient centrifugation. Lastly, we shall also determine if simultaneous Neisseria gonorrhoeae infection modulates C. trachomatis infection of human endometrial cells.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Bacteriology and Mycology Subcommittee 1 (BM)
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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