Titel: iPSC-derived macrophages as a treatment approach for multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis patients
ID: 184/MPP
Art: Abstractautor
Session: P1
Microbial Pathogenesis (FG MP)

Referent: Tim Wüstefeld (Hannover)

Abstract - Text

According to the World Health Organization, infectious diseases of the lower respiratory tract are among the top five causes of death with 3.1 million reports in 2012. Especially infections with Pseudomonas aeruginosa (P. aeruginosa), a leading pathogen in causing nosocomial infections, are associated with substantial mortality. Since P. aeruginosa is equipped with a strong antibiotic resistance machinery, the number of infections caused by multidrug-resistant P. aeruginosa is constantly growing. In light of the emerging threat of antibiotic resistant bacteria, new and alternative therapeutic approaches are highly desirable. Similarly, new therapeutic interventions are needed for bacterial pathogens which are refractory to antibiotic treatment and commonly seen in patients suffering from cystic fibrosis (CF). In CF, P. aeruginosa is linked to progressive loss of lung function and very severe courses. In our current project, we therefore plan to investigate the phagocytic capacity of macrophages targeting different (antibiotic resistant) P. aeruginosa derived from various CF clinical isolates. We aim to use induced pluripotent stem cell technology (iPSC) to gain insights into macrophage-pathogen interaction with the aim to establish an innovative cell therapy approach for chronic P. aeruginosa infections. For this ambitious aim, we will first set up cell-based co-culture assays using the P. aeruginosa reference strain PA14 and different clinical isolates of CF patients to elucidate the phagocytic capacity of iPSC-derived macrophages. Hannover Medical School can rely on a unique strain collection of sequential clinical isolates of its patients, previously isolated right from the individual onset of infection over the whole infection period. Patient courses had been described in detail (Klockgether et al. 2018). Phagocytosis and behavior of iPSC-derived macrophages will be analyzed using selected sequential isolates in cell culture and plating experiments measuring colony forming units. Also, pro- and anti-inflammatory cytokine analysis will be conducted to evaluate the therapeutic potential of iPSC-derived macrophages.

Taken the potential to generate scalable amounts of iPSC-derived macrophages, a successful completion of this proposal will allow assessing the capacity of these cells to phagocytose antibiotic resistant P. aeruginosa and may lay the foundation for a new cell-based therapy targeting chronic bacterial infections of the lower respiratory tract.