Delineating the dynamics of neutrophil response in multiple inflammatory stimuli and its consequences

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PhD; 2023; Centre for biosystems science and engineering

In this thesis, we investigate the regulation of neutrophils, an important component of the immune system, and its implications on inflammation and pathological conditions. We use biomaterial implants to induce chronic sterile inflammation in mice and examine the effects on neutrophil production rates, maturation times, and lifespan in various tissue compartments. We demonstrate that in case where inflammation leads to emergency granulopoiesis (EG), we observe increased neutrophils progenitors, reduced maturation time in the bone marrow, reduced lifespan in circulation, and prolonged residence time at the inflammatory site. These changes aim to maintain high neutrophil numbers at the site of inflammation while keeping the circulating neutrophil count constant. However, this also results in an increase in immature neutrophils in circulation. Next, we explore the response of neutrophils to a second inflammation in mice undergoing EG.