TIPE2 serves as a molecular switch of phagocytosis during infection

Phagocytosis is essential for host defense against microbial pathogens and clearance of apoptotic cells. TIPE2 (TNF-α-induced protein 8 like-2) is a newly described inhibitor of immune receptor signaling. We report here that TIPE2 knockout (KO) mice were resistant to lethal Listeria monocytogenes infection, cleared the bacteria more rapidly and effectively, and produced lower levels of inflammatory cytokines than wild type (WT) mice. TIPE2 KO macrophages had enhanced phagocytic activity as compared to WT macrophages. TIPE2 regulated phagocytosis at multiple steps, including internalization and phagosome maturation as well as bacteria killing. Importantly, Toll-like receptor activation dramatically downregulated TIPE2 expression while significantly enhanced phagocytic activity of macrophages. These results indicate that TIPE2 may function as a molecular switch of phagocytosis during infection. In response to pathogens, down-regulation of TIPE2 promotes phagocytosis, which in turn eliminates the pathogens.