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  • Review Article
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Immune responses to Listeria monocytogenes

Nature Reviews Immunology volume 4, pages 812–823 (2004)Cite this article

Key Points

  • Listeria monocytogenes is a Gram-positive, intracellular bacterial pathogen that invades the cytosol of infected cells.

  • Tumour-necrosis factor (TNF) and interferon-γ are essential for in vivo immune defence against primary infection with L. monocytogenes.

  • TNF- and inducible nitric-oxide synthase (iNOS)-producing dendritic cells (TipDCs) are recruited to sites of L. monocytogenes infection in the spleen in a CC-chemokine receptor 2-dependent manner.

  • MyD88 (myeloid differentiation primary-response protein 88)-mediated signals, and presumably Toll-like-receptor-mediated signals, are essential for clearance of primary infection with L. monocytogenes.

  • CD8+ T cells provide long-term protective immunity against re-infection with L. monocytogenes. Maintenance of CD8+ T-cell memory requires CD4+ T cells.

  • Full induction of protective immunity requires infection with live, cytosol-invasive L. monocytogenes.

  • The primary immune response to infection with L. monocytogenes is mediated by two main CD8+ T-cell subpopulations: one is restricted by MHC class Ia molecules, and the other is restricted by the MHC class Ib molecule H2–M3.

  • H2–M3-restricted T cells make an important contribution to the primary immune response to L. monocytogenes.

Abstract

Listeria monocytogenes is a Gram-positive bacterium that is often used to study the mammalian immune response to infection because it is easy to culture, is relatively safe to work with and causes a highly predictable infection in laboratory mice. The broad application of this mouse model has resulted in a torrent of studies characterizing the contributions of different cytokines, receptors, adaptors and effector molecules to resistance against infection with Listeria monocytogenes. These studies, which are yielding one of the most comprehensive pictures of the 'battle' between host and microorganism, are reviewed here.

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Figure 1: The pathogenesis of cellular Listeria monocytogenes infection.
Figure 2: Innate immune activation by virulent Listeria monocytogenes is a multistep process.
Figure 3: CD8+ T-cell responses to primary and secondary infection.
Figure 4: Presentation of Listeria monocytogenes-derived antigens to CD8+ T cells.

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Authors and Affiliations

  1. Department of Medicine, Infectious Disease Service, Memorial Sloan-Kettering Cancer Center, Immunology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, 10021, New York, USA

    Eric G. Pamer

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DATABASES

Entrez Gene

4-1BB

ActA

CCL2

CCR2

CCR5

CD11c

CD40

CD137L

complement receptor 3

H2–M3

ICOS

IFN-γ

IFN-regulatory factor 3

iNOS

internalin A

internalin B

IRAK-M

LLO

LRG47

lymphotoxin-β receptor

MyD88

p47 phox

p50 subunit of NF-κB

p60

RIP2

TLR2

TLR5

TNF

TNFRp55

TRAIL

Infectious Disease Information

Listeria monocytogenes

FURTHER INFORMATION

Eric Pamer's laboratory

Glossary

MONOCYTOSIS

A marked increase in the number of monocytes that are circulating in the bloodstream. It occurs following infection with some pathogens.

CHORIOAMNIONITIS

An infection of placental tissues (the chorion and amnion) during pregnancy. It usually extends to infection of the intra-uterine foetus.

PHOSPHOLIPASES

Enzymes that are produced by some pathogenic bacteria. They hydrolyse phospholipids including phosphatidylinositol and phosphatidylcholine.

HEXOSE-PHOSPHATE TRANSLOCASE

(Hpt). A bacterially encoded membrane protein that transports phosphorylated hexose carbohydrates from the cytosol of the host cell into the bacterium.

ATTENUATED

A reduced capacity to cause disease. This can occur because of auxotrophy or loss of virulence.

SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE

Mice with this defect do not have B or T cells.

NUDE MICE

Mice with a mutation that causes both hairlessness and defective formation of the thymus, resulting in a lack of mature T cells.

CROSS-PRESENTATION

The initiation of a CD8+ T-cell response to an antigen that is not present within antigen-presenting cells (APCs). This exogenous antigen must be taken up by APCs and then re-routed to the MHC class I pathway of antigen presentation.

PEST SEQUENCE

Protein sequence that is found in unstable cytosolic proteins that contain unusually high frequencies of proline (P), glutamine (E), serine (S) and threonine (T) residues. It results in rapid, proteasome-mediated degradation.

PROTEASOME-MEDIATED DEGRADATION

Most of the degradation of cytosolic and nuclear proteins in eukaryotic cells is catalysed by multisubunit proteases known as proteasomes.

IMMUNODOMINANT EPITOPES

Epitopes present in a complex mixture of proteins (such as provided by a whole virus, tumour cell or bacterium) that induce strong T-cell responses.

CD4+CD25+ REGULATORY T CELLS

A specialized subset of CD4+ T cells that can suppress the responses of other T cells. These cells are characterized by the expression of the α-chain of the interleukin-2 (IL-2) receptor (also known as CD25). In some cases, suppression has been associated with the secretion of IL-10, transforming growth factor-β or both of these cytokines.

N-FORMYL METHIONINE

Bacteria initiate protein synthesis with N-formyl methionine, a modified form of the amino acid methionine, which is used by prokaryotic cells. The only eukaryotic proteins that contain N-formyl methionine are those encoded by mitochondria.

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Pamer, E. Immune responses to Listeria monocytogenes. Nat Rev Immunol 4, 812–823 (2004). https://doi.org/10.1038/nri1461

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