Fig. 3

When gut-derived PAMPs are exposed to hepatic macrophages, the macrophages are polarized and form large numbers of M1-like macrophages that mainly produce proinflammatory cytokines such as IL-1β, TNF, and IL-6; some M2-like macrophages typically produce IL-10 and play a role in anti-inflammatory reactions. Inflammasomes are activated in hepatic macrophages and in response to pathogen infections and tissue injury. Moreover, neutrophils are attracted to the liver by chemotactic factors, such as CXCL1 and CXCL2 derived from KCs, and released NETs participate in removal of pathogens and toxins. Platelet recruitment is also critical for limiting bacterial infection, and platelets that interact with KCs play a crucial role in fighting against bacterial infection. However, when an inappropriate immune response or overwhelming inflammation occurs with high levels of DAMP formation and proinflammatory cytokine production in the liver, notable hepatocyte injury, macrophage autophagy, and apoptosis occur. Hepatic macrophages are supplemented by KC proliferation and circulating monocyte recruitment and differentiation. CXCL, chemokine (C-X-C motif) ligand; DAMPs, damage-associated molecular patterns; IL, interleukin; KCs, Kupffer cells; NETs, neutrophil extracellular traps; PAMPs, pathogen-associated molecular patterns; TNF, tumor necrosis factor