Understanding lung dendritic cell function in resistance to influenza: from mouse to human

Three times over the last century, the influenza A virus has caused major global pandemics with significant rates of disease and death. Even the less fierce, seasonal flu epidemics have their cost: recent estimates show that, in the United States, they cost the economy some 100 billion dollars. What’s more, since small changes to the virus’s genetic makeup occur constantly, our vaccines must be updated every year as we try to stay one step ahead of this pathogen.
Understanding better how the flu virus interacts with the human immune system would answer questions about how it manages to evade our defenses. This is the goal of a team led by Prof. Matthew Collin of Newcastle University. They started their investigation at the virus’s first point of contact with our immune system: the lung dendritic cells.
The main role of dendritic cells (DC) is to take up foreign particles invading the body and process them for presentation on the cell surface—a signal that will activate other cells to launch an immune response. Using innovative bioinformatics tools, Collin’s lab identified two subsets of human DC that appear to have distinct functions in resisting infection with influenza A. This was first observed in mouse models, which will also make it possible to determine the exact role of the DC subsets in fighting off the virus. To accomplish this, Collin will use a method called inducible depletion, meaning he will artificially trigger the regression of each of the mouse dendritic cell subsets in question, to determine the effect their absence may have on the immune response to influenza A.
The conclusions drawn from such mouse studies will need to be translated back into humans in order to shed light on the virus’s ability to cause disease in people. Additional tests to achieve this important step will be carried out on human DC grown in the lab, as well as an innovative “humanized” mouse model with human lung DC grafts.
Ultimately, Collin’s research should clarify to a much greater extent the precise role of our lung dendritic cells in launching a defense against influenza A infection. With this knowledge, more relevant strategies could be developed for designing vaccines—a current need that is sure to remain with us into the future.