Chlamydiae are Gram-negative obligate intracellular bacteria that infect mainly epithelial mucosa and have been implicated in a broad spectrum of diseases in mammals and birds. Chlamydia (C.) psittaci is the causative agent of psittacosis, a widespread infection in psittacine birds and domestic poultry. Transmission of C. psittaci to humans and the zoonotic potential of this infection have been documented by different studies. In natural hosts, clinical outcomes of C. psittaci-infection range from clinical silence to severe or even mortal illness. Consistent with the intracellular localization of chlamydia, T cell-mediated immune responses against this bacteria are observed in infected organisms. Dendritic cells (DCs) are among the first immune cells encountered by chlamydia. It is thought that cytotoxic CD8+ T cells primed by MHC I/antigen-presentation of infected DCs play an important role in the immune response against the bacterial pathogen. Despite the crucial role of DCs and CD8+ T cells during chlamydial infection, the mechanism by which chlamydial antigens are processed and presented on cell surface MHC I molecules is only poorly understood. We could demonstrate that fundamental cellular recycling and maintenance mechanisms, known as autophagy, play a critical role in chlamydial antigen processing in infected DCs. During our studies we discovered a novel pathway of MHC I cross-presentation that is initiated with a host cellular attack physically disrupting the bacterial vacuole, involves autophagy to collect cytosolic chlamydia and concludes with multi-step antigenic processing in separate cellular compartments. The findings provide new insights into the cellular mechanisms of antigen presentation as well as cell autonomous defense and have important implications for the future design of therapeutic strategies.
In contrast to chlamydia, coxiella is able to survive in autophagic compartments. Different studies suggest a functional role of autophagy in the establishment of cellular infections with coxiella. In this context, we are interested to investigate the influence of coxiella on cell autonomous defense of infected cells as well as the immune subversion of MHC-mediated antigen processing and presentation.
- Bacterial cell infection
- Metabolic reprogramming of APCs
- Cell autonomous immunity
- MHC-mediated antigen presentation & cross-presentation