Crosstalk between liver macrophages and gut microbiota: An important component of inflammation-associated liver diseases

Abstract

Hepatic macrophages have been recognized as primary sensors and responders in liver inflammation. By processing host or exogenous biochemical signals, including microbial components and metabolites, through the gut-liver axis, hepatic macrophages can both trigger or regulate inflammatory responses. Crosstalk between hepatic macrophages and gut microbiota is an important component of liver inflammation and related liver diseases, such as acute liver injury (ALI), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). This review summarizes recent advances in knowledge related to the crosstalk between hepatic macrophages and gut microbiota, including the therapeutic potential of targeting hepatic macrophages as a component of gut microecology in inflammation-associated liver diseases.

Keywords: gut microbiota; gut-liver axis; inflammation; innate immunity; liver disease; macrophage.

FIGURE1

Outlines of the roles of hepatic macrophages in liver inflammation. Kupffer cells (KCs) can engage and response to different signals including pro-inflammatory damage-associated molecular patterns (DAMP) and microbe-associated molecular patterns (MAMP) or anti-inflammatory MAMP and microbial metabolites. In the pro-inflammatory response, KCs can secrete pro-inflammatory agents such as IL-1β and CCL2, which are responsible to initiate liver inflammation and recruit other immune cells to infiltrate liver. Another main subset of hepatic macrophage, monocyte-derived macrophages (MoMφs), is also an important component in the inflammatory infiltration. Besides, in the anti-inflammatory response, KCs can secrete anti-inflammatory agents and regulate inflammatory signaling and response.

FIGURE 2

Regulating pathways of the microbial intervention on the inflammatory phenotype in hepatic macrophages and liver inflammation.