Research Areas
The Jenne lab is interested in the innate immune response to infection. With intravital microscopy, we are able to directly visualize, in real-time, the host immune response, “seeing” leukocytes, platelets and pathogens within live animals. Using this approach, we are able to track and characterize the interactions between host immune cells, the invading pathogen, and surrounding tissues. Our studies can be broadly grouped into three general research themes:
The interaction between innate immunity and coagulation.
Platelets are often thought of with respect to their role in blood clotting and the prevention of bleeding; however, platelets are important players in the host immune response. Platelets can mediate leukocyte recruitment and activation, can induce the production of Neutrophil Extracellular Traps (NETs), and can have direct antimicrobial activity. Interestingly, these immune functions do not seem to be completely uncoupled from the role platelets in coagulation. Often, severe infection leads to inappropriate activation of coagulation, resulting in the formation of small clots within the bloodstream. These micro-thrombi have the potential to become lodged in small blood vessels, blocking blood flow, leading to tissue damage and organ dysfunction. Of particular interest are infections mediated by multidrug-resistant bacteria such as Staphylococcus aureus or viruses such as influenza A. Infections with these pathogens associated with severe disease and great propensity to activate coagulation, leading to tissue damage and organ failure. Our lab aims to better understand the interactions between immunity and coagulation in an effort to limit inappropriate clotting, preserve blood flow, prevent tissue damage and improve patient outcomes.
The innate immune response to viral infection.
Viral infections have classically been considered to be the domain of the adaptive immune system; high-affinity, neutralizing antibodies and cytotoxic “killer” lymphocytes. Often overlooked is the potent and robust innate, inflammatory response that viruses elicit. We have shown a coordinated response by neutrophils and platelets that can protect host tissues from viral infection. We have also shown that this inflammatory response has great potential damage host tissues. We are currently trying to understand this balance between protection from infection and self-inflicted collateral damage. Using intravital microscopy to characterize the cellular interactions, adhesion molecules and effector mechanism involved in mounting an effective host immune response we are able to study systemic and localized viral infections of the lung, skin and liver. Additionally, we seek to understand how viruses are detected, captured, and cleared from the body in most infections, while in others, such as Hepatitis B, the virus is able to evade clearance to set up chronic infection. Overall, the aim of this research is to identify novel therapeutic and vaccine strategies that will limit collateral damage caused by inflammation while enabling optimal anti-viral immunity.
In addition to studying viruses as a pathogen, we are also actively studying viruses as a tool. Oncolytic viruses represent an exciting potential therapy for the treatment of cancer and several clinical trials are underway using this novel “tool”. Using intravital microscopy, we are studying how these oncolytic viruses are delivered, by the bloodstream, to the tumor and how these infectious particles interact with components of host immunity, modulating the local tissue microenvironment, and supporting recruitment of leukocytes to the tumor site.
Effect of vaccination on the ability of the host to detect, capture and kill pathogens.
Both natural and high affinity antibodies (generated through vaccination) improve the ability of the host to recognize and neutralize pathogens. Using intravital microscopy we are able to characterize how these antibodies also enhance the clearance of pathogens from the blood and tissues by resident macrophage. By studying the effect of changing the specific antibody (high vs low affinity, isotype, presence or absence of complement activation) we aim to better understand how vaccination can be optimized to efficiently facilitate the clearance of pathogens while simultaneously limiting collateral inflammation and tissue damage. We are also engaged in developing and optimizing novel vaccine platforms, seeking to develop approaches to generate immunity that is both durable and cross-protective against numerous viral variants.