Article
Antigen processing via autophagy--not only for MHC class II presentation anymore?
Viral Immunobiology, Institute of Experimental Immunology, University Hospital of Zürich, Switzerland.
Current opinion in immunology (impact factor:
10.88).
02/2010;
22(1):89-93.
DOI:10.1016/j.coi.2010.01.016
pp.89-93
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Autophagy in protists.
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ABSTRACT: Autophagy is the degradative process by which eukaryotic cells digest their own components using acid hydrolases within the lysosome. Originally thought to function almost exclusively in providing starving cells with nutrients taken from their own cellular constituents, autophagy is in fact involved in numerous cellular events including differentiation, turnover of macromolecules and organelles, and defense against parasitic invaders. During the last 10-20 years, molecular components of the autophagic machinery have been discovered, revealing a complex interactome of proteins and lipids, which, in a concerted way, induce membrane formation to engulf cellular material and target it for lysosomal degradation. Here, our emphasis is autophagy in protists. We discuss experimental and genomic data indicating that the canonical autophagy machinery characterized in animals and fungi appeared prior to the radiation of major eukaryotic lineages. Moreover, we describe how comparative bioinformatics revealed that this canonical machinery has been subject to moderation, outright loss or elaboration on multiple occasions in protist lineages, most probably as a consequence of diverse lifestyle adaptations. We also review experimental studies illustrating how several pathogenic protists either utilize autophagy mechanisms or manipulate host-cell autophagy in order to establish or maintain infection within a host. The essentiality of autophagy for the pathogenicity of many parasites, and the unique features of some of the autophagy-related proteins involved, suggest possible new targets for drug discovery. Further studies of the molecular details of autophagy in protists will undoubtedly enhance our understanding of the diversity and complexity of this cellular phenomenon and the opportunities it offers as a drug target.Autophagy 04/2011; 7(2):127-58. · 7.45 Impact Factor -
Article: Autophagy in herpesvirus immune control and immune escape.
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ABSTRACT: Autophagy delivers cytoplasmic constituents for lysosomal degradation, and thereby facilitates pathogen degradation and pathogen fragment loading onto MHC molecules for antigen presentation to T cells. Herpesviruses have been used to demonstrate these novel functions of autophagy, which previously has been primarily appreciated for its pro-survival role during starvation. In this review, we summarize recent findings how macroautophagy restricts herpesvirus infections directly, how macroautophagy and chaperone mediated autophagy contribute to herpesviral antigen presentation on MHC molecules, and which mechanisms herpesviruses have developed to interfere with these pathways. These studies suggest that herpesviruses significantly modulate autophagy to escape from its functions in innate and adaptive immunity.Herpesviridae. 01/2011; 2(1):2. -
Article: Autophagy Regulates IL-23 Secretion and Innate T Cell Responses through Effects on IL-1 Secretion.
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ABSTRACT: Autophagy controls IL-1β secretion by regulating inflammasome activation and by targeting pro-IL-1β for degradation. In this article, we show that inhibition of autophagy, either with the PI3K inhibitors 3-methyladenine, wortmannin, and LY294002 or with small interfering RNA against autophagy proteins augmented the secretion of IL-23 by human and mouse macrophages and dendritic cells in response to specific TLR agonists. This process occurred at the transcriptional level and was dependent on reactive oxygen species and IL-1R signaling; it was abrogated with an IL-1R antagonist or with IL-1-neutralizing Abs, whereas treatment with either rIL-1α or IL-1β induced IL-23 secretion. Dendritic cells treated with LPS and 3-methyladenine secreted enhanced levels of both IL-1β and IL-23, and supernatants from these cells stimulated the innate secretion of IL-17, IFN-γ, and IL-22 by γδ T cells. These data demonstrate that autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL-1 and its consequential effects on IL-23 secretion.The Journal of Immunology 09/2012; 189(8):4144-53. · 5.79 Impact Factor
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Keywords
additional autophagic mechanisms
autophagic pathways
class II antigen processing
display lysosomal products
endocytosed proteins
immunologists
intracellular
major histocompatibility complex
MHC
MHC class
MHC class II molecules
present intracellular substrates
T cells
