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  • Review Article
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Mechanisms of pathogen entry through the endosomal compartments

Nature Reviews Molecular Cell Biology volume 7, pages 495–504 (2006)Cite this article

Key Points

  • The endocytic pathway is composed of two sorting stations, the early and late endosomes, and the lysosomes. Internalized molecules first enter in early endosomes from where they can be recycled to the plasma membrane or transported to late endosomes. Once in late endosomes, molecules can be sorted to the trans-Golgi network, selectively transported to the plasma membrane or packaged into lysosomes, where degradation occurs.

  • Large particles, such as bacteria, are taken up by phagocytosis and are eventually degraded in phagolysosomes — this process helps to clear the extracellular environment of pathogens. Because the nascent phagosomes are unable to kill microorganisms, phagosomal maturation occurs through sequential interactions with early and late endosomes and finally with lysosomes.

  • Pathogens and their products have evolved ways to use and benefit from the endocytic entry routes into the cell. To avoid degradation in lysosomes, pathogens must escape from endosomes before these fuse with lysosomes or they must prevent phagosomal maturation.

  • Some pathogenic agents have acquired the capacity to hijack intrinsic endosomal properties to avoid the lysosomes. For example, the anthrax toxin and vesicular stomatitis virus seem to (mis-)use mechanisms that regulate the dynamics of multivesicular endosomes.

  • Other pathogens, and in particular bacteria, have adopted strategies, which can be very diverse, to change the properties of endosomes and lysosomes. Common themes include the modification of the phosphoinositide content to change the apparent identity of organelles. This can result in the prevention of phagosomal maturation at early or later stages, the modification of lipid-raft properties by bacterial products and alterations of phagosomal and endosomal localization and motility.

  • Trypanosoma cruzi, a parasitic protozoa, uses yet another strategy to enter the cell. As opposed to most other pathogens, T. cruzi does not avoid lysosomes, but requires them for efficient infection. Fusion of the parasite with the lysosomes is required for the release of the parasite into the cytoplasm, where replication occurs.

Abstract

Several pathogens — bacteria, viruses and parasites — must enter mammalian cells for survival, replication and immune-system evasion. These pathogens generally make use of existing cellular pathways that are designed for nutrient uptake, receptor downregulation and signalling. Because most of these pathways end in lysosomes, an organelle that is capable of killing microorganisms, pathogens have developed remarkable means to avoidinteractions with this lytic organelle.

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Figure 1: Schematic view of the endocytic pathway.
Figure 2: Multivesicular endosomes and viral nucleocapsids.
Figure 3: Pathogens and toxins in the endocytic pathway.

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Acknowledgements

We apologize to those whose studies could not be mentioned due to space constraints. Support was from the Swiss National Science Foundation (to J.G. and F.G.v.d.G.), National Institute of Health (to F.G.v.d.G.), Howard Hughes Medical Institute (to F.G.v.d.G.) and the International Human Frontier Science Program (to J.G.).

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  1. Department of Biochemistry, University of Geneva, 30 quai Ernest Ansermet, Geneva, 1211, Switzerland

    Jean Gruenberg

  2. Department of Microbiology and Molecular Medicine, University of Geneva, 1 rue Michel Servet, Geneva, 1211, Switzerland

    F. Gisou van der Goot

  3. Institute of Global Health, Ecole Polytechnique Fdrale de Lausanne, SVStation 15, Lausanne, 1015, Switzerland

    F. Gisou van der Goot

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  1. Jean Gruenberg
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Glossary

Caveolae

Flask-shaped invaginations of the plasma membrane that are coated with the protein caveolin and are endocytosed in a clathrin-independent manner.

Endosomal carrier vesicles

Transport intermediates between early and late endosomes. They are multivesicular and are therefore also called multivesicular bodies (MVBs).

Mannose-6-phosphate (Man6P) receptors

The receptors that carry lysosomal enzymes that harbour a mannose-6-phosphate moiety to lysosomes.

Major histocompatibility complexes (MHC) class II

Immune complexes that present peptides, which are derived from extracellular antigens, to T cells.

Toll-like receptors

Type I transmembrane proteins that recognize perpetual infectious threat and activate innate responses.

Innate immunity

Nonspecific mechanisms by which pathogens are recognized by cells.

Adaptive immune response

A specific immune response to a given antigen that includes antibody production and the selection of T cells.

MHC class II compartment

A late endosomal compartment that is present in professional antigen-presenting cells and that has specific functions that are distinct from protein degradation. They are enriched in MHC class II proteins and other molecules that are involved in peptide processing, loading and editing and localize to the compartment where most antigen processing and peptide loading occurs.

Exosomes

A term to describe intralumenal vesicles from multivesicular endosomes when they are secreted into the extracellular medium upon fusion of the organelle with the plasma membrane.

Phagosome

The membrane bound compartment that results from the phagocytosis of large particles.

Listeriosis

A rare bacterial infection that is acquired by eating undercooked infected meat or from proximity to infected live animals.

Salmonellosis

Food-borne infection with Salmonella species, which results in diarrhoea, fever and abdominal cramps.

Brucellosis

Infection with Brucella species that is also called Malta or Mediterranean fever. It frequently causes abortions in animals and remittent fever in humans.

Cyclodextrins

Compounds that contain Dglucose units that are joined through α 1–4 linkages in such a way as to form a ring.

Auxotroph

A microorganism that is unable to synthesize a particular organic compound that is required for its growth.

Dendritic cell

The most antigen-presenting cell of the human body.

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Gruenberg, J., van der Goot, F. Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol 7, 495–504 (2006). https://doi.org/10.1038/nrm1959

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  • DOI: https://doi.org/10.1038/nrm1959

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