PD186 - RECOMBINANT HUMAN PLASMA GELSOLIN SIGNIFICANTLY INCREASES PHAGOCYTOSIS OF CANDIDA AURIS CELLS BY HUMAN NEUTROPHILS (ID 477)
Abstract
Backgrounds:
Impairment of innate immune response in immunocompromised subjects, predispose to recurrent and life-threatening fungal infections. Decrease of plasma gelsolin (pGSN) concentration (hypogelsolinemia) that was observed in the blood of patients with septic shock, tissue injuries, different chronic diseases and cancers, highlight its crucial role in severe medical conditions. Recent studies demonstrated the ability of pGSN to stimulate phagocytosis in bacterial-infected mice. Nevertheless, the data about involvement of human plasma gelsolin in host response to fungal infections are still very limited.
Methods
To isolate neutrophils blood obtained from healthy volunteers was centrifuged in Polymorphprep density gradient. To assess the effect of pGSN on neutrophils function, cells were serum starved for 1h, preincubated with pGSN, washed and infected with C. auris. As control fungal cells were also added to serum starved neutrophils simultaneously with corresponding concentration of pGSN. Internalization of pHrodo zymosan particles and extracellular DNA release was evaluated using a IncuCyte SX1 Live Imaging System. Process of NETosis was monitored using MPO activity and observed using a confocal microscope. Fluorometric assay was used to determine ROS formation. Alternation of inflammatory response upon pGSN treatment of C. auris infected neutrophils was monitored with use of magnetic bead–based assay.
Results:
Preincubation of human neutrophils with pGSN significantly improved uptake of Candida auris cells with simultaneous reduction of NETotic death as well as inflammatory response.
Conclusions/Learning Points:
The number of agents with potent antifungal activity is significantly limited, and those that are approved for clinical use are often very toxic or insufficiently effective, which justify and motivate research and development of new methods using molecules with novel and/or alternative mechanisms of action. Recombinant human pGSN due to its immunomodulatory properties is a candidate worth consideration.
The work was supported by the National Science Centre, Poland, under research project Preludium bis 1, no UMO-2019/35/O/NZ6/02807.
