Mpeg1-KO Mouse

Mpeg1, also known as Perforin-2 (PRF2), is an ancient metazoan protein belonging to the Membrane Attack Complex/Perforin (MACPF) branch of the MACPF/Cholesterol Dependent Cytolysin (CDC) superfamily of pore-forming proteins (PFPs). It is highly expressed in macrophages and other phagocytes and is postulated to play a role in immunity, especially in the destruction of phagocytosed microbes [1,3-5,7].

Mpeg1 knockout mouse models have shown that relative to wild-type controls, Mpeg1 knockout mice suffer significantly higher mortality rates when challenged with gram-negative or-positive pathogens [3,4,5]. This indicates that Mpeg1 endows phagocytes with potent bactericidal capability [4]. However, another study using a new Mpeg1 mutant allele Mpeg1tm1.1Pib found that mice homozygous for this allele are not abnormally susceptible to bacterial or viral infection, and show no perturbation in bacterial killing in vitro [2]. Also, Mpeg1-deficient mice fail to efficiently prime CD8+ T cells to cell-associated antigens, revealing its role in cytosolic entry of antigens during cross-presentation [6].

In conclusion, Mpeg1 appears to be involved in antibacterial immunity and antigen presentation based on model-based research. Gene knockout mouse models have been crucial in highlighting its potential role in susceptibility to microbial infections, especially those caused by intracellular bacteria [1,3,4,5]. However, there are still some conflicting findings regarding its essentiality in antibacterial and antiviral immunity, which warrants further investigation.

References:

1. Bayly-Jones, Charles, Pang, Siew Siew, Spicer, Bradley A, Whisstock, James C, Dunstone, Michelle A. 2020. Ancient but Not Forgotten: New Insights Into MPEG1, a Macrophage Perforin-Like Immune Effector. In Frontiers in immunology, 11, 581906. doi:10.3389/fimmu.2020.581906. https://pubmed.ncbi.nlm.nih.gov/33178209/

2. Ebrahimnezhaddarzi, Salimeh, Bird, Catherina H, Allison, Cody C, Whisstock, James C, Bird, Phillip I. 2022. Mpeg1 is not essential for antibacterial or antiviral immunity, but is implicated in antigen presentation. In Immunology and cell biology, 100, 529-546. doi:10.1111/imcb.12554. https://pubmed.ncbi.nlm.nih.gov/35471730/

3. Merselis, Leidy C, Jiang, Shirley Y, Nelson, Stanley F, Munson, George P, Butte, Manish J. 2020. MPEG1/Perforin-2 Haploinsufficiency Associated Polymicrobial Skin Infections and Considerations for Interferon-γ Therapy. In Frontiers in immunology, 11, 601584. doi:10.3389/fimmu.2020.601584. https://pubmed.ncbi.nlm.nih.gov/33224153/

4. Merselis, Leidy C, Rivas, Zachary P, Munson, George P. 2021. Breaching the Bacterial Envelope: The Pivotal Role of Perforin-2 (MPEG1) Within Phagocytes. In Frontiers in immunology, 12, 597951. doi:10.3389/fimmu.2021.597951. https://pubmed.ncbi.nlm.nih.gov/33692780/

5. McCormack, Ryan M, Szymanski, Eva P, Hsu, Amy P, Podack, Eckhard R, Holland, Steven M. 2017. MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections. In JCI insight, 2, . doi:10.1172/jci.insight.89635. https://pubmed.ncbi.nlm.nih.gov/28422754/

6. Rodríguez-Silvestre, Pablo, Laub, Marco, Krawczyk, Patrycja A, Borner, Georg H H, Kozik, Patrycja. 2023. Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells. In Science (New York, N.Y.), 380, 1258-1265. doi:10.1126/science.adg8802. https://pubmed.ncbi.nlm.nih.gov/37347855/