Hepatocytes are constantly engaged in  diverse homeostatic activities including processing of gut-derived products, regulation of whole body metabolism and detoxification events. Hepatocytes also play a major role in host defence by mediating systemic inflammation and innate immunity through the production of acute phase proteins and complement components, and responding locally to infection by hepatotropic viruses via pattern recognition receptor activation, such as RIG-I and TLR3. Bona fide immune cells alter their metabolism to meet the metabolic demands of an induced immune response. Reactive oxygen species (ROS), generated through a metabolic switch, have been identified as a key link  between the immune response and the metabolic state of the cell. Whether this process also occurs in other cell types, such as hepatocytes, remains unclear. Here, using two hepatoma cell lines, HepG2 and Huh7 cells, treated with transfected polyI:C, we sought to explore the link between the metabolic state of hepatocytes and their ability to mount an antiviral immune response.  Following treatment with polyI:C, we saw an increase in CXCL10 and IFN-b gene expression and protein production. To assess the metabolic state of the polyI:C treated cells, we used fluorescence lifetime imaging microscopy (FLIM) and Seahorse real-time cellular flux analysis. Following treatment with polyI:C cellular oxygen consumption was decreased. Using MitoSOX as ROS-fluorescent probe, ROS levels increased after treatment with polyI:C. Modulating ROS levels through scavengers (N-acetyl cysteine) and oxidants drugs (Rotenone), we were able to regulate the amplitude of the antiviral response, indicating a role for ROS in shaping the antiviral immune response in hepatocytes.

Hepatocytes are constantly engaged in  diverse homeostatic activities including processing of gut-derived products, regulation of whole body metabolism and detoxification events. Hepatocytes also play a major role in host defence by mediating systemic inflammation and innate immunity through the production of acute phase proteins and complement components, and responding locally to infection by hepatotropic viruses via pattern recognition receptor activation, such as RIG-I and TLR3. _Bona fide_ immune cells alter their metabolism to meet the metabolic demands of an induced immune response. Reactive oxygen species (ROS), generated through a metabolic switch, have been identified as a key link  between the immune response and the metabolic state of the cell. Whether this process also occurs in other cell types, such as hepatocytes, remains unclear. Here, using two hepatoma cell lines, HepG2 and Huh7 cells, treated with transfected polyI:C, we sought to explore the link between the metabolic state of hepatocytes and their ability to mount an antiviral immune response.  Following treatment with polyI:C, we saw an increase in CXCL10 and IFN-b gene expression and protein production. To assess the metabolic state of the polyI:C treated cells, we used fluorescence lifetime imaging microscopy (FLIM) and Seahorse real-time cellular flux analysis. Following treatment with polyI:C cellular oxygen consumption was decreased. Using MitoSOX as ROS-fluorescent probe, ROS levels increased after treatment with polyI:C. Modulating ROS levels through scavengers (N-acetyl cysteine) and oxidants drugs (Rotenone), we were able to regulate the amplitude of the antiviral response, indicating a role for ROS in shaping the antiviral immune response in hepatocytes.

RIG-I induced reactive oxygen species drive metabolic changes that modulate the antiviral immune response in hepatocytes

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.