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M1 protein-dependent intracellular trafficking promotes persistence and replication of Streptococcus pyogenes in macrophages.

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-κB 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.

journal_name

J Innate Immun

journal_title

Journal of innate immunity

authors

Hertzén E,Johansson L,Wallin R,Schmidt H,Kroll M,Rehn AP,Kotb M,Mörgelin M,Norrby-Teglund A

doi

10.1159/000317635

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

534-45

issue

6

eissn

1662-811X

issn

1662-8128

pii

000317635

journal_volume

2

pub_type

杂志文章

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