UC Merced

Bacterial infections of the mucosal epithelium initiate inflammation of the local tissues, which leads to changes in the molecular profile of the extracellular milieu, including increases in extracellular ATP, and its ecto-enzymatic and hydrolytic degradation products ADP and adenosine. Extracellular ATP and adenosine function as signaling molecules at purinergic receptors which have been shown to regulate several key aspects of immune cell function. Information has been quite limited, however, on how this may alter bacterial growth in the inflamed tissue. Here we demonstrate that stimulation of Chlamydia trachomatis infected epithelial cells with micromolar extracellular ATP, ADP and adenosine significantly impairs growth of the bacteria. The response to adenosine is mediated by the A2b receptor, while the effects of ATP and ADP suggest involvement of P2X4 receptors. Chlamydial growth is reversibly inhibited, and the bacteria return to normal growth kinetics following removal of the stimulus. This suggests that extracellular adenosine and adenine nucleotides are important for local control of C. trachomatis at infected mucosal epithelium, and that further characterization of the intracellular mechanisms employed by the host could lead to improved methods of treating this important pathogen.