Innate Immunity and Infection

HSV-2 

The innate immune system is a critical component in combating infection. It provides a quick initial immune response to bacterial or viral challenges and shapes and stimulates the adaptive immune response that is ultimately responsible for clearing the infection. As the repertoire of cells and cytokines in the innate immune environment is vast and diverse, a few areas have become prominent research focal points within our lab.


Interleukin-15:

We are currently investigating the signalling pathway of IL-15 and its effects on the innate immune environment during viral infection. While it is well-known that IL-15 signals through lymphocytes through a trans-presentation mechanism, in which IL-15 is presented by IL-15 receptor-α to the IL-2β  and common-γ-chain receptors on lymphocytes, a different mechanism of IL-15 signalling and activation may be occurring in immune cells of myeloid lineage. As a widely expressed cytokine with a crucial impact during infection, research that focuses on understanding IL-15 will have fundamental impacts on health and human disease.

Natural Killer Cells:

We are exploring the antiviral effect of natural killer cells in response to a number of viral infections, including influenza and HSV-2. We are particularly interested in the mechanisms that maintain, activate, and regulate natural killer cells in the context of viral infection.

TLR ligands:

TLR ligands have the potential to modulate and shape the induction of the innate immune response to viral infection. We are interested in understanding the protective role of TLR ligands during infection.


HCV

Currently there is no vaccine available against hepatitis C infection. Even though recent advances have provided effective treatments for HCV, they are extremely expensive.

HCV primarily targets human liver epithelial cells, known as hepatocytes. NK cells are enriched among liver resident lymphocytes and comprise about 30% of the lymphocyte population. Their natural enrichment in the liver and their ability to eliminate virally infected hepatocytes places NK cells in a key position among effector cells in HCV infection.

Our hypothesis is that NK cells play a main role in the elimination of HCV. We know that the treatment of hepatocytes with IL-15 and IFN-γ can induce anti-HCV effects however, a significant obstacle to further understanding host-HCV interactions is the lack of relevant animal models.

Therefore, the generation of Autologous Double Humanized Mice with human liver and human immune cells provides us with a unique opportunity to study the interaction of innate and adaptive immunity with HCV infected human liver cells in a relevant in vivo model.