Anti-Chlamydia trachomatis Host Defence Arsenal Within the Cervicovaginal Environment

<i>Chlamydia trachomatis</i> has a significant impact on public health, especially among adolescents and young women; it primarily affects urogenital epithelial cells, leading to cervicitis and urethritis, with >90% of cases showing no symptoms. Consequently, chlamydial infections are commonly misdiagnosed, and, if untreated, they may result in severe reproductive sequelae including infertility. A better understanding of <i>C. trachomatis</i> cell biology and bacterial-host cell interactions may be helpful to identify strategies able to counter its transmission among the population, as well as its dissemination in reproductive tissues, reducing the risk of developing severe reproductive sequelae. Therefore, the present review aims to summarize the evidence on the interplay between <i>C. trachomatis</i> and the host defence factors within the cervicovaginal environment. The sophisticated strategies employed by this clinically significant pathogen to counteract these mechanisms are also discussed. In the literature, the main defence factors include the microbiota dominated by <i>Lactobacillus crispatus</i> and several molecules like lactoferrin, able to protect the cervicovaginal microenvironment against <i>C. trachomatis</i> through several mechanisms (e.g., EB coaggregation and competitive exclusion, as well as anti-inflammatory activity). However, the major player in clearing chlamydial infections remains the interferon-gamma (IFN-γ) produced by natural killer and T cells, via the depletion of critical nutrients for <i>C. trachomatis</i> such as tryptophan, or via the ubiquitylation and destruction of chlamydial inclusions.