Liver cirrhosis is the build-up of scar tissue resulting in impaired liver function. It can have different causes including alcohol abuse, obesity and viral hepatitis. For reasons that we do not fully understand, patients with cirrhosis are more susceptible to infections. In fact, 50% of hospitalised patients with liver cirrhosis and infections die, highlighting the scale of this problem. Macrophages (MFs) are immune cells present in every tissue of the body that function to eliminate pathogens. In the liver, one subset of MFs, the Kupffer cells (KCs) are perfectly equipped to do this. Moreover, they are positioned in the bloodstream meaning they are one of the first cells to see and respond to circulating pathogens but their precise roles have not been studied. In cirrhosis, KCs are also reduced in number, being replaced by distinct MF subtypes. Our preliminary data demonstrate that both KCs and these other MFs from the cirrhotic liver respond less efficiently to infection compared with their healthy counterparts. Thus, we hypothesize that the altered MF landscape in cirrhosis is one mechanism driving the increased susceptibility to infection. Here, we aim to test this by examining how the different MFs respond to infection in the presence and absence of cirrhosis. Using novel mouse models specifically targeting the distinct MF populations, we will tease apart the mechanisms through which MFs exert their effects and attempt to manipulate these, to limit infection.