M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-kappa B signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury. Copyright (C) 2010 S. Karger AG, Basel

Detaljer

Författare
  • Erika Hertzen
  • Linda Johansson
  • Robert Wallin
  • Heike Schmidt
  • Mirko Kroll
  • Anders P. Rehn
  • Malak Kotb
  • Matthias Mörgelin
  • Anna Norrby-Teglund
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området

Nyckelord

Originalspråkengelska
Sidor (från-till)534-545
TidskriftJournal of Innate Immunity
Volym2
Utgivningsnummer6
StatusPublished - 2010
PublikationskategoriForskning
Peer review utfördJa