Marco, known as Macrophage receptor with collagenous structure, is a member of scavenger receptor class A (SR-A) [2]. It plays a crucial role in the immune response, triggering innate and adaptive immune responses, bridging the two types of immunity, and eliminating pathogens [2]. It is also involved in multiple functions such as adhesion, migration, phagocytosis, and cytokine secretion [2]. MARCO can interact with various immune-related pathways including TNF/NFκB signaling, KRAS signaling, PI3K/AKT/mTOR pathway, IL-6-STAT3 signaling, TGFβ pathway, and p53 pathway [1].

In animal experimental models, functional ablation of Marco+ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH, indicating that Marco+ macrophages limit excessive liver inflammation [3]. In the context of porcine reproductive and respiratory syndrome virus (PRRSV), MARCO acts as a host restriction factor, inhibiting viral proliferation by intensifying virus-induced apoptosis [4]. In chikungunya virus (CHIKV) infection, MARCO is involved in determining whether a vertebrate serves as an amplification or dead-end host [5]. Blocking MARCO+ tumor-associated macrophages can improve anti-PD-L1 therapy of hepatocellular carcinoma by promoting the activation of STING-IFN type I pathway [6]. MARCO+ alveolar macrophages contribute to age-related lung fibrosis in a CCL6-dependent manner [7].

In conclusion, Marco is essential for immune-related functions and is involved in various disease conditions. Studies using animal models have revealed its role in liver inflammation, viral infections, cancer immunotherapy, and age-related lung fibrosis, highlighting its potential as a therapeutic target in these disease areas.