Dysfunctional macrophages along the gut-liver axis: a driver of infection in cirrhosis.

Patients with cirrhosis are highly susceptible to infections which could trigger a vicious cycle of events, including hepatic decompensation, organ failure, and increased mortality. These infections often originate from the gastrointestinal tract when bacteria breach the intestinal barrier and disseminate towards the liver. Macrophages are key immune cells along the gut-liver axis, where they play a crucial role in preserving barrier integrity under homeostatic conditions. In cirrhosis, however, macrophage specialization, spatial organization, and antimicrobial functions are disrupted. In this review, we discuss the progress made in understanding the heterogeneity of intestinal and hepatic macrophages, emphasizing their distinct ontogeny and the specialized niches that dictate their function. We describe the roles these populations perform in health, particularly in lining critical cellular barriers within the gut-liver axis, followed by how these processes are compromised in the context of cirrhosis. Finally, we explore how therapeutic approaches might target dysregulated macrophages or restore their barrier-protective functions in advanced liver disease.