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Autophagy in innate and adaptive immunity against intracellular pathogens

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Abstract

Autophagy delivers cytoplasmic constituents for lysosomal degradation. Recent studies have demonstrated that this pathway mediates resistance to pathogens and is targeted for immune evasion by viruses and bacteria. Lysosomal degradation products, including pathogenic determinants, are then surveyed by the adaptive immune system to elicit antigen-specific T cell responses. CD4+ T helper cells have been shown to recognize nuclear and cytosolic antigens via presentation by major histocompatibility complex (MHC) class II molecules after autophagy. Furthermore, some sources of natural MHC class II ligands display characteristics of autophagy substrates, and autophagosomes fuse with late endosomes, in which MHC class II loading is thought to occur. Although MHC class II antigen processing via autophagy has so far mainly been described for professional antigen-presenting cells like B cells, macrophages, and dendritic cells, it might be even more important for cells with less endocytic potential, like epithelial cells, when these express MHC class II at sites of inflammation. Therefore, autophagy might contribute to immune surveillance of intracellular pathogens via MHC class II presentation of intracellular pathogen-derived peptides.

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Abbreviations

APC:

Antigen-presenting cell

Atg:

Autophagy-related gene

CLIP:

Class II-associated Ii-derived peptide

CTL:

Cytotoxic T lymphocyte

DRiP:

Defective ribosomal product

EBNA1:

Epstein–Barr virus nuclear antigen 1

EBV:

Epstein–Barr virus

Hsc70:

Heat shock cognate protein 70/73

HLA:

Human leukocyte antigen

Ii:

Invariant chain

LAMP:

Lysosomal-associated membrane protein

MHC:

Major histocompatibility complex

MIIC:

MHC class II-containing compartment

Mtb:

Mycobacterium tuberculosis

Th:

T helper cell

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Acknowledgements

We thank the National Cancer Institute (R01CA108609), the Arnold and Mabel Beckman Foundation, and the Alexandrine and Alexander Sinsheimer Foundation for supporting our research (to C.M.). D.S. is a recipient of a predoctoral fellowship from the Schering Foundation.

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Authors and Affiliations

  1. Laboratory of Viral Immunobiology, and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY, USA

    Dorothee Schmid & Christian Münz

  2. Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

    Jörn Dengjel, Oliver Schoor & Stefan Stevanovic

  3. Laboratory of Viral Immunobiology, The Rockefeller University, 1230 York Avenue, New York, NY, 10021, USA

    Christian Münz

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  1. Dorothee Schmid
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  2. Jörn Dengjel
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  4. Stefan Stevanovic
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  5. Christian Münz
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Correspondence to Christian Münz.

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Schmid, D., Dengjel, J., Schoor, O. et al. Autophagy in innate and adaptive immunity against intracellular pathogens. J Mol Med 84, 194–202 (2006). https://doi.org/10.1007/s00109-005-0014-4

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