(BSc Lenoir-Rhyne, PhD Wake Forest)
The co-evolution between an animal and pathogen is a fundamental aspect of Biology. Animals face selective pressure from a diverse group of potential pathogens, including viruses, bacteria, fungi and protozoan and metazoan parasites. Because of such pressure, animals have evolved intricate defense mechanisms, for which the success of the host response resides in its ability to appropriately recognize the threat, efficiently respond to and eliminate the pathogen, and rapidly resolve the inflammation inherent to a targeted immune response.
To recognize an invading pathogen in a timely manner, macrophages—sentinel cells of the immune system—constantly monitor all environmental interfaces within the host. To be effective, these cells must recognize foreign substances, but also further distinguish between those that may be infectious vs. foreign materials that pose no direct threat, such as dust or pollen. Upon recognition of an infectious agent, macrophages, along with other professional antigen-presenting cells, carefully orchestrate the deployment of an appropriate immune response, and upon rejection of the pathogen, these cells then coordinate the resolution of the respective inflammatory response.
This process of immune recognition, response and resolution must be tightly regulated to maintain homeostasis within an animal. Indeed, pathology and the resulting morbidity within an animal host often becomes manifest from a dysregulated macrophage response. Such dysregulation may result in extreme inflammation whereby much of the host pathology is self-inflicted, as is observed during highly-pathogenic influenza virus infections. Alternatively, the dysregulated macrophage response may result in systemic immune-suppression, such as that observed during parasitic helminth infection. In this case, not only is the host incapable of clearing the parasitic infection, but also maintains a compromised ability to respond to a secondary infection.
This focus of this research program is to better understand the mechanisms responsible for the development of a dysregulated macrophage response. To do so, we will investigate monocyte differentiation in vitro, and also employ two model infections in the murine host, 1) influenza virus, in which we previously demonstrated that host pathology was predominantly due to macrophage-driven inflammation, and 2) Taenia crassiceps, a parasitic helminth that naturally drives a suppressive phenotype in macrophages.