Control Mechanisms Governing the Infectivity of Chlamydia trachomatis for HeLa Cells: Modulation by Cyclic Nucleotides, Prostaglandins and Calcium

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Abstract
C. trachomatis causes common infections of the eyes and genital tract in man. The mechanism by which this obligate intracellular bacterium is taken into epithelial cells is unclear. The concept that chlamydial infection of HeLa cells is under bidirectional cyclic nucleotide control, with cGMP acting as a stimulator and cAMP as an inhibitor was supported. Treatment of the HeLa cells with the divalent cation ionophore A23187, with carbamoylcholine or with prostaglandins known to increase the concentration of endogenous cGMP, also increased host cell susceptibility to chlamydial infection. cGMP was only effective if added at or before chlamydial inoculation, suggesting that its main effect was on chlamydial uptake. The stimulatory effect of cGMP, but not antagonism by cAMP, was abolished if the cells were first treated with any of 4 different inhibitors of prostaglandin synthesis, suggesting a critical role for endogenous prostaglandin synthesis. Centrifugation of chlamydiae on to host cells was followed by a rapid increase in the mobility of Ca2+ across the cell membrane. The interrelationships of these observations and the possibility that chlamydiae and other intracellular pathogens might evoke alterations in host cell prostaglandin and cyclic nucleotide concentrations to aid their own uptake are discussed.