Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion

Nat Commun. 2024 Oct 7;15(1):8663. doi: 10.1038/s41467-024-53060-4.

Abstract

Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.

MeSH terms

  • Animals
  • Bacterial Toxins / immunology
  • Bacterial Toxins / metabolism
  • COVID-19* / immunology
  • COVID-19* / virology
  • Female
  • Heat-Shock Proteins / metabolism
  • Hemolysin Proteins / metabolism
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Humans
  • Immune Evasion
  • Immunity, Innate
  • Interferon Type I* / immunology
  • Interferon Type I* / metabolism
  • Kupffer Cells* / immunology
  • Listeria monocytogenes* / immunology
  • Listeria monocytogenes* / physiology
  • Listeriosis* / immunology
  • Listeriosis* / microbiology
  • Liver / immunology
  • Liver / microbiology
  • Liver / virology
  • MAP Kinase Signaling System / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils* / immunology
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / physiology
  • Spleen / immunology

Substances

  • Bacterial Toxins
  • Heat-Shock Proteins
  • Hemolysin Proteins
  • hlyA protein, Listeria monocytogenes
  • Interferon Type I