Streptococcus pneumoniae PepO promotes host anti-infection defense via autophagy in a Toll-like receptor 2/4 dependent manner

Virulence. 2020 Dec;11(1):270-282. doi: 10.1080/21505594.2020.1739411.

Abstract

Macrophage is essential for host anti-bacterial defense by directly eliminating invading microbes and inducing a series of immune reactions. Here we identified a Streptococcus pneumoniae protein, PepO, as a TLR2/TLR4 bi-ligand. We found that PepO enhances macrophage unspecific phagocytosis and bactericidal activity, which is related to the induction of autophagy in macrophage, for the inhibition of autophagy significantly decreased the phagocytosis and bactericidal activity of PepO-treated macrophage. We confirmed that these effects of PepO are dependent on interacting with both TLR2 and TLR4. The tlr2 or tlr4 deficiency partially abolished the effect of PepO while tlr2/tlr4 deficiency abolished it completely. In vivo study demonstrated that PepO reduced the bacteria load in WT mice significantly, while the depletion of macrophage or tlr2/tlr4 deficiency abrogated the effect of PepO. Our findings suggested the therapeutic potential of PepO and provided experimental evidence for immunotherapy against infectious disease.

Keywords: Bacterial infection; autophagy; immunotherapy; macrophage; toll-like receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Bacterial Load
  • Bacterial Proteins / genetics*
  • Cytokines
  • Endopeptidases / genetics*
  • Female
  • Host Microbial Interactions*
  • Immunity, Innate
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phagocytosis
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / immunology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*

Substances

  • Bacterial Proteins
  • Cytokines
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Endopeptidases
  • PepO protein, Streptococcus pneumoniae

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81701572] to Z.H. and the National Natural Science Foundation of China [grant number 31700804] to L.Y.S.