Engagement of heterogeneous nuclear ribonucleoprotein M with listeriolysin O induces type I interferon expression and restricts Listeria monocytogenes growth in host cells

Immunobiology. 2012 Oct;217(10):972-81. doi: 10.1016/j.imbio.2012.01.009. Epub 2012 Jan 14.

Abstract

Listeriolysin O (LLO) is a key virulence factor secreted by the Gram-positive, facultative intracellular pathogen Listeria monocytogenes (LM). Its role in host cell response is still not very clear. Using pull-down assay, mass spectrometry analysis and immunoprecipitation approaches, we found that LLO interacted with heterogeneous nuclear ribonucleoprotein M (hnRNPM), a member of RNA splicing complex apparatus, and the binding domain of LLO for hnRNP M was located between amino acids 26 and 176. Knockdown of hnRNP M inhibited LLO-induced activation of IFN-α, IFN-β and AP-1 promoters and enhanced LM growth in host cells. Thus, engagement of hnRNP M with LLO induces type I interferon expression and restricts LM growth in host cells, suggesting a critical role of hnRNP M in LLO-induced immune responses in host cells. These findings will contribute to further understandings of the molecular mechanisms underlying the host defense against LM infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / genetics
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / metabolism
  • Cell Line
  • Gene Expression Regulation*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / immunology*
  • Heat-Shock Proteins / metabolism
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / immunology*
  • Hemolysin Proteins / metabolism
  • Hemolysis / immunology
  • Heterogeneous-Nuclear Ribonucleoprotein Group M / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group M / metabolism*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Interferon Type I / genetics*
  • Interferon Type I / metabolism
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Transport
  • RNA Interference
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Toxins
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • Heterogeneous-Nuclear Ribonucleoprotein Group M
  • Interferon Type I
  • Recombinant Proteins
  • hlyA protein, Listeria monocytogenes