New insights into the pathogenesis and treatment of chlamydial infections

Chlamydiae are obligate intracellular Gram-negative bacteria with a unique biphasic developmental cycle, alternating between infectious elementary bodies and replicative reticulate bodies. However, when exposed to stressful conditions such as iron deprivation and IFN-gamma exposure, they fail to complete their developmental cycle generating morphologically aberrant reticulate bodies called persistent forms, which remain viable but non-infectious inside the host-cell for a long time and are difficult to eradicate with antibiotics. Chlamydiae cause a broad spectrum of diseases. Chlamydia pneumoniae causes community-acquired pneumonia and other respiratory tract infections, while Chlamydia trachomatis is the leading cause of sexually transmitted diseases all over the world and of trachoma in developing countries. More importantly, these pathogens may cause chronic sequelae. In fact, C. pneumoniae infections may be associated to atherosclerosis, whereas C. trachomatis infections lead to ectopic pregnancy, obstructive infertility and reactive arthritis. These sequelae could result from the inflammatory state induced by the persistent forms. In our research, we studied in vitro different aspects of chlamydial pathogenesis and treatment in C. pneumoniae and C. trachomatis, achieving the following results. In C. pneumoniae, in order to investigate the atherogenic process, we set up a model of foam cell induction by means of macrophages infection. In this model, we highlighted for the first time the C. pneumoniae-dependent production of IL-17A, a cytokine recently reported as proatherogenic. Moreover, we investigated the protective effects of resveratrol, a natural polyphenol known to exert antioxidant, cholesterol-lowering and anti-inflammatory effects. Resveratrol is able to avoid foam cell formation in macrophages exposed to high levels of lipoproteins, with possible applications in the prevention of atherosclerosis. In C. trachomatis, we assessed the antichlamydial activity of the essential oil of Mentha suaveolens, in an effort to find out new means to prevent sexually transmitted diseases