Mpeg1 is not essential for antibacterial or antiviral immunity, but is implicated in antigen presentation

Salimeh Ebrahimnezhaddarzi, Catherina H. Bird, Cody C. Allison, Daniel E. Tuipulotu, Xenia Kostoulias, Christophe Macri, Michael D. Stutz, Gilu Abraham, Dion Kaiserman, Siew Siew Pang, Si Ming Man, Justine D. Mintern, Thomas Naderer, Anton Y. Peleg, Marc Pellegrini, James C. Whisstock, Phillip I. Bird

Research output: Contribution to journalArticleResearchpeer-review

Abstract

To control infections phagocytes can directly kill invading microbes. Macrophage-expressed gene 1 (Mpeg1), a pore-forming protein sometimes known as perforin-2, is reported to be essential for bacterial killing following phagocytosis. Mice homozygous for the mutant allele Mpeg1tm1Pod succumb to bacterial infection and exhibit deficiencies in bacterial killing in vitro. Here we describe a new Mpeg mutant allele Mpeg1tm1.1Pib on the C57BL/6J background. Mice homozygous for the new allele are not abnormally susceptible to bacterial or viral infection, and irrespective of genetic background show no perturbation in bacterial killing in vitro. Potential reasons for these conflicting findings are discussed. In further work, we show that cytokine responses to inflammatory mediators, as well as antibody generation, are also normal in Mpeg1tm1.1Pib/tm1.1Pib mice. We also show that Mpeg1 is localized to a CD68-positive endolysosomal compartment, and that it exists predominantly as a processed, two-chain disulfide-linked molecule. It is abundant in conventional dendritic cells 1, and mice lacking Mpeg1 do not present the model antigen ovalbumin efficiently. We conclude that Mpeg1 is not essential for innate antibacterial protection or antiviral immunity, but may play a focused role early in the adaptive immune response.

Original languageEnglish
Number of pages18
JournalImmunology and Cell Biology
DOIs
Publication statusAccepted/In press - 26 Apr 2022

Keywords

  • dendritic cells
  • inflammation
  • macrophage expressed gene
  • monocytes and macrophages
  • mpeg1
  • perforin 2

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