AP-1 as the determinant of replicative and persistent intracellular C. pneumoniae infection

• Applicant: Professor Dr. Jan Rupp
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2006 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 29407680

Chlamydia pneumonias is an obligate intracellular pathogen which effectively infects different types of cells. The capacity of Chlamydiae to induce replicative or persistent infection is attributed to the infected cell type and dependent on host cell apoptosis and survival. In cells which allows replicative C. pnewnoniae infection (epithelial cells) apoptosis is delayed for up to 72 h until the intracellular developmental cycle is completed, the host cell is destroyed and infectious Chlamydiae are released. In contrast, in cells in which C. pneumoniae can establish a persistent infection (blood monocytes) replication is drastically reduced and host cell survival is prolonged for more than 6 days. Although some C. pneumoniae induced pro-inflammatory and proliferative signaling pathways share similarities, cell type specific mechanisms involved in the regulation of replication and persistence of C. pneumoniae are unknown. Pro- and anti-apoptotic properties in different cells are determined by the specific composition of AP-1 hetero- and homodimers. We could recently show C. pneumoniae to induce the AP-1 signaling cascade in replication competent epithelial cells and in persistently infected blood monocytes. The aim of the study is to investigate the role of C. pneumoniae induced AP-1 complexes in replicative and persistent infection and to analyze their functional role in host cell survival. We will focus on direct interactions between C. pneumoniae induced AP-1 complexes and the Bcl-2 family member Mcl-1 as a key regulator of cell apoptosis or anti- apoptosis. Therapeutical strategies directed against C. pneumoniae induced signaling cascades in specific host cells may reveal new options for the treatment of persistent C. pneumoniae infections which are resistant to currently available antibiotic therapies.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1131: Life Inside Cells
• Participating Person: Professor Dr. Ger van Zandbergen