A5: Impact of microenvironmental factors on neutrophil effector functions directed against Salmonella (S.) enterica serovar Typhimurium

A5: Impact of microenvironmental factors on neutrophil effector functions directed against Salmonella (S.) enterica serovar Typhimurium

Neutrophils are at the frontline of pathogen defense and equipped with a highly potent antimicrobial arsenal. Upon infection, extravasated neutrophils often face extreme conditions and have to function in complex and unpredictable environments. How neutrophils acutely integrate tissular signals to adapt their immune effector functions accordingly, has not yet been addressed. We have recently established a novel imaging platform that allows for the dynamic visualization of the dynamic behavior of extravascular immune effector cells with high spatial and temporal resolution, yet within the physiological context of an intact tissue (in situ peritoneal imaging). This experimental setup allows for the detailed analysis of acute neutrophil anti-pathogen activities under a variety of microenvironmental conditions. We will study neutrophilic anti-pathogen response, using an ex vivo tissue-bioimaging platform (explanted peritoneal serosa with pre-elicited, neutrophils). Here, static and dynamic high-resolution microscopy (confocal, 2-photon) will be combined with in situ metabolic monitoring and further RNAseq, metabolomic and proteomic approaches. Our approach will enable us to modify parameters of the tissue milieu (e.g., pH, oxygen saturation, ion content, tonicity) and thus directly study the impact of microenvironmental factors on effector functions of neutrophils in a living tissue.

Project A5_Uderhardt

Supervisor