Mpeg1, also known as Perforin-2, is a pore-forming protein belonging to the Membrane Attack Complex/Perforin (MACPF) family. It is highly expressed in macrophages and other phagocytes and is postulated to play a role in immunity. It is thought to be involved in the destruction of phagocytosed microbes, and its expression is upregulated in response to pro-inflammatory signals like TNFα and LPS [2].

Mice homozygous for the mutant allele Mpeg1tm1Pod succumb to bacterial infection and show deficiencies in bacterial killing in vitro, while mice homozygous for the new allele Mpeg1tm1.1Pib on the C57BL/6J background are not abnormally susceptible to bacterial or viral infection, and show no perturbation in bacterial killing in vitro. Mpeg1-deficient mice do not present the model antigen ovalbumin efficiently, suggesting it may play a role in the early adaptive immune response [1]. Mpeg1 knockout mice have significantly higher mortality rates when challenged with gram-negative or -positive pathogens, as phagocytosed bacteria can persist and replicate within their phagocytes [3,4]. Heterozygous Mpeg1+/- mice display an intermediate killing ability compared with Mpeg1 WT and Mpeg1 -/- mice [5].

In conclusion, Mpeg1 is likely an intracellular pore-forming immune effector. While some studies suggest it may not be essential for innate antibacterial or antiviral immunity, model-based research, especially using Mpeg1 knockout mouse models, has shown its importance in the destruction of phagocytosed microbes and in the early adaptive immune response. Mutations in Mpeg1 are associated with an increased susceptibility to certain infections in both animals and humans, highlighting its significance in infectious disease [1,2,3,4,5].