Polymorphonuclear neutrophils (PMNs) are a major subset of innate immune cells that are part of the first line immune defence against bacterial infections. Chlamydia trachomatis, a major human pathogen, manipulate PMNs during the infection process and subvert them to become unresponsive to a broad range of stimuli, including Chlamydia themselves. Even more surprising, although PMNs are extremely short lived, Chlamydia not only survive PMN exposure but can also surprisingly exploit PMN itself as host cell for replication. It remains completely unclear how PMNs are converted to host cells for obligate intracellular bacteria.
Incidences of sexually transmitted diseases (STI) have increased during the past decades with a concomitant rapid spread of antibiotic resistant bacteria. Chlamydia trachomatis is the most frequent cause of bacterial STIs with more than 130 millions per year. These infections often remain asymptomatic and are consequently not diagnosed and treated, resulting in the subsequent development of severe chronic pathologies and an enormous economic burden for health systems. The reason for the asymptomatic nature of chlamydial infection is currently unknown but may well be connected to the subversion of PMNs.
We identified a chlamydial secreted protease (CPAF) to be the bacterial effector responsible for preventing the activation of the non-stimulated PMNs. In addition, the chlamydial secreted deubiquitinase Cdu1 is required for intracellular adaptation of Chlamydia, indicating that PMNs may posses antibacterial cell-autonomous defence strategies based on the host ubiquitin system. The objective of the current project is the detailed investigation of how Chlamydia subvert PMNs in the course of infection.
