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Medientyp:
E-Artikel
Titel:
M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages
Beteiligte:
Hertzén, Erika;
Johansson, Linda;
Wallin, Robert;
Schmidt, Heike;
Kroll, Mirko;
Rehn, Anders P.;
Kotb, Malak;
Mörgelin, Matthias;
Norrby-Teglund, Anna
Erschienen:
S. Karger AG, 2010
Erschienen in:Journal of Innate Immunity
Sprache:
Englisch
DOI:
10.1159/000317635
ISSN:
1662-811X;
1662-8128
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p><i>Streptococcus pyogenes</i> 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 <i>S. pyogenes</i> 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 <i>S. pyogenes</i> within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of <i>S. pyogenes</i> 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-ĸB 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.</jats:p>