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Autophagy in Infection and Immunity pp 189–215Cite as

Autophagy in Immunity Against Intracellular Bacteria

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

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.

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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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Acknowledgments

John H. Brumell, Ph.D., holds an Investigators in Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund. Ju Huang was supported by a Restracomp Fellowship from the Hospital for Sick Children and is the recipient of a CAG/CIHR/CCFC postdoctoral fellowship administered by the Canadian Association of Gastroenterology. We thank Dr. Cheryl Birmingham for discussion and critical reading of the manuscript.

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Authors and Affiliations

  1. Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada, M5G 1X8

    Ju Huang & John H. Brumell

  2. Department of Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, ON, Canada, M5S 1A8

    John H. Brumell

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  1. Ju Huang
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  2. John H. Brumell
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Correspondence to John H. Brumell .

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Editors and Affiliations

  1. Southwestern Medical Center, University of Texas, Harry Hines Blvd. 5323, Dallas, 75390-9113, U.S.A.

    Beth Levine

  2. Research Inst. Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka, 565-0871, Japan

    Tamotsu Yoshimori

  3. Health Sciences Center, University of New Mexico, Camino de Salud NE., 915, Albuquerque, 87131, U.S.A.

    Vojo Deretic

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© 2009 Springer-Verlag Berlin Heidelberg

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Huang, J., Brumell, J.H. (2009). Autophagy in Immunity Against Intracellular Bacteria. In: Levine, B., Yoshimori, T., Deretic, V. (eds) Autophagy in Infection and Immunity. Current Topics in Microbiology and Immunology, vol 335. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00302-8_9

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