Autophagy in Infection and Immunity pp 189-215

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 335)

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Autophagy in Immunity Against Intracellular Bacteria

Chapter

Abstract

Autophagy is an innate immune defense mechanism against various intracellular bacterial pathogens, such as Salmonella enterica serovar Typhimurium (S. typhimurium), Listeria monocytogenes and Shigella flexneri. S. typhimurium uses type three secretion systems (T3SSs) to invade mammalian cells and replicate in Salmonella-containing vacuoles (SCVs). A small population of intracellular S. typhimurium is targeted by autophagy shortly after infection. Evidence suggests that these bacteria are present within SCVs that have been damaged by high levels of T3SS activity. Autophagy limits the growth of S. typhimurium in host cells. Therefore, autophagy can be considered to protect the cytosol of eukaryotic cells from bacterial colonization. L. monocytogenes secretes the pore-forming cytolysin listeriolysin O (LLO) to disrupt the phagosome and escape into the cytosol, where it acquires actin-based motility. Autophagy can target L. monocytogenes in the cytosol under specific experimental conditions. However, L. monocytogenes utilizes several virulence factors to evade being killed by the autophagy system. A newly appreciated population of L. monocytogenes undergoes slow growth in specialized vacuoles termed spacious Listeria-containing phagosomes (SLAPs), the formation of which requires bacterial LLO and host autophagy. In the cytosol, S. flexneri can also be a target for autophagy in the absence of a T3SS effector, IcsB, that normally impairs the interaction between Atg5 and wild-type bacteria. Therefore, autophagy can recognize intracellular bacteria in a variety of ways, leading to different fates for these bacteria in host cells. The inefficient autophagy of enteric bacteria in genetically compromised individuals may contribute to the pathogenesis of Crohn’s disease.

Abbreviations

CD

Crohn’s disease

EEA1

Early endosome antigen 1

ER

Endoplasmic reticulum

GEF

Guanine nucleotide exchange factor

IRG

Immunity-related GTPase

LAMP-1

Lysosome-associated membrane protein 1

LLO

Listeriolysin O

3-MA

3-Methyladenine

M6PR

Mannose-6-phosphate receptor

MEF

Mouse embryonic fibroblast

NLR

NOD-like receptor

NOD

Nucleotide-binding oligomerization domain

p.i.

Postinfection

PLC

Phospholipase C

SCID

Severe combined immunodeficiency

SCV

Salmonella-containing vacuole

SLAP

Spacious Listeria-containing phagosome

SNP

Single nucleotide polymorphism

SPI

Salmonella pathogenicity island

T3SS

Type three secretion system

TLR

Toll-like receptor

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Cell Biology ProgramHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Molecular Genetics and Institute of Medical ScienceUniversity of TorontoTorontoCanada

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