(483f) Navigating the Matrix: How Neutrophils Interact with Their Microenvironment | AIChE

(483f) Navigating the Matrix: How Neutrophils Interact with Their Microenvironment


Calo, C. - Presenter, University of Delaware
Hind, L., University of Colorado Boulder
Richardson, I., University of Colorado Boulder
Two of the greatest global health crises of our time, the COVID-19 pandemic and the rise in deaths due to antimicrobial-resistant infections, have demonstrated the cost associated with our inability to predict or affect the immune system’s response to infection. The innate immune system, the fast-acting branch of the immune system, is the body’s first line of defense against infection and plays an important role in maintaining healthy tissue. Unfortunately, the signals and interactions that regulate the innate immune response to infection remain poorly understood. While many studies have investigated the chemical signals that drive the neutrophil response to infection, few studies have looked at the role of the physical environment in regulating neutrophil function. Following infection, neutrophils bind to and migrate along the vessel endothelium before extravasating into the tissue environment. This interaction has been shown to alter neutrophil activation, migration, and lifetime. Furthermore, properties such as protein density and substrate stiffness are known to affect endothelial cell stiffness, adhesion surface protein expression, and secretion profiles. Neutrophil migration and force generation are also known to increase in response to increases in tissue stiffness. We, therefore, sought to study how the physical environment affects the neutrophil response to infection both directly through ECM-neutrophil signaling and indirectly through interactions with an endothelium.

One obstacle in studying the innate immune response is understanding how the milieu of signals present in the infectious microenvironment drive the neutrophil response to infection. This is, in part, due to the experimental systems used to study the immune system. The innate immune response to infection is typically studied using animal models that do not truly represent human biology or simplistic in vitro techniques that do not account for interactions between innate immune cells and other cell populations or the physical environment. To overcome this challenge, we have developed a physiologically relevant infection-on-a-chip system that recapitulates many important aspects of the infectious microenvironment including a model endothelial blood vessel, primary human innate immune cells, and an extracellular matrix. Using this model, we have investigated the role of the ECM in regulating neutrophil function.