Grant: Project Grant

The liver filters and processes all the stuff that you eat. This includes food, drugs, alcohol and most importantly the bacterial products and the few bacteria that sneak from the intestine into the blood stream. Inside the liver is a filtering system like no other: millions of immune cells whose job it is to sit in the little blood vessels and catch bacteria. This system is not fully functional at birth especially in premature babies. We have a way of going inside the body and watching these immune cells catch bacteria using a special intravital microscope. Using this system we have found that at birth these immune cells are sitting outside the blood vessels and need to get into the blood vessels to be able to catch bacteria. It takes 3 weeks for all these immune cells to get inside the blood vessels and efficiently catch bacteria. We will elucidate the mechanisms by which this happens and examine whether the microbiome helps with this process by looking at mice with no microbiome. These specific liver immune cells called Kupffer cells seem to enter the liver before birth and then remain there. If a Kupffer cell dies then the other Kupffer cells replicate and make more. However, if many or all Kupffer cells die than new cells come in from the bone marrow and make new Kupffer cells that require some training before they become bona fide Kupffer cells. Using imaging we can watch how long before these cells can catch bacteria. We will see if the microbiome can expedite this situation and whether it matters whether you are a boy or a girl young or old etc. Finally, we will look at what happens to these cells during fibrosis in which the liver gets scarred and how the Kupffer cells function ie., their ability to kill bacteria. Liver disease will be the next epidemic with no treatment available (25% of Canadians have liver scarring) so we need to find ways of treating these patients.