Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Biomed Environ Sci. 2020 May 20;33(5):295-305. doi: 10.3967/bes2020.041.

Abstract

Objective: Interferon-induced transmembrane protein 3 (IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.

Methods: We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer (NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/- and wild-type mice.

Results: Ifitm3-/- mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/- mice during acute influenza infection.

Conclusions: Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/- mice.

Keywords: IFITM3; Immune response; Influenza; NK cells.

MeSH terms

  • Acute Disease
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Influenza, Human / virology*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • Rodent Diseases / virology*

Substances

  • Membrane Proteins
  • fragilis protein, mouse