Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis

Key Points The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and antigen presentation. Extensive crosstalk between autophagy and inflammatory signalling cascades ensures a robust immune response tow...

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Published in	Nature reviews. Immunology Vol. 16; no. 11; pp. 661 - 675
Main Author	Cadwell, Ken
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.11.2016 Nature Publishing Group
Subjects	631/250/2152 631/250/262 631/80/82/39 Adaptive Immunity Amino acids Animals Antigen presentation Autophagosomes - immunology Autophagosomes - metabolism Autophagy Autophagy (Cytology) Autophagy - immunology Bacteria Biomedicine Care and treatment Cellular signal transduction Communicable diseases Cytokines Defense Disease Susceptibility Health aspects Homeostasis Homeostasis - immunology Host-Pathogen Interactions - immunology Humans Immune response Immunity Immunity, Innate Immunology Infections Inflammation - immunology Inflammation - metabolism Inflammatory diseases Observations Pathogens Pattern recognition Pattern recognition receptors Proteins review-article Signal Transduction Tumor necrosis factor-TNF Viruses New York United States > US
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Abstract	Key Points The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and antigen presentation. Extensive crosstalk between autophagy and inflammatory signalling cascades ensures a robust immune response towards pathogens while avoiding collateral damage to the host. Several chronic inflammatory disorders are associated with autophagy dysfunction. Pathways that induce autophagy, such as those downstream of pattern recognition receptors, are conversely subject to regulation by autophagy. Autophagy can increase and decrease different components of the same inflammatory signalling cascade in a context-dependent manner. Many immune-related functions of conserved autophagy proteins reflect non-canonical functions of the autophagy machinery, representing new opportunities for therapeutic intervention. This article provides a comprehensive overview of the general functions of autophagy in immunity, the interactions between autophagy and immune signalling pathways and the role of autophagy–immune crosstalk in multicellular immune responses and disease. Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.
AbstractList	Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases. Key PointsThe cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and antigen presentation.Extensive crosstalk between autophagy and inflammatory signalling cascades ensures a robust immune response towards pathogens while avoiding collateral damage to the host. Several chronic inflammatory disorders are associated with autophagy dysfunction.Pathways that induce autophagy, such as those downstream of pattern recognition receptors, are conversely subject to regulation by autophagy.Autophagy can increase and decrease different components of the same inflammatory signalling cascade in a context-dependent manner.Many immune-related functions of conserved autophagy proteins reflect non-canonical functions of the autophagy machinery, representing new opportunities for therapeutic intervention.This article provides a comprehensive overview of the general functions of autophagy in immunity, the interactions between autophagy and immune signalling pathways and the role of autophagy–immune crosstalk in multicellular immune responses and disease. The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and antigen presentation. Extensive crosstalk between autophagy and inflammatory signalling cascades ensures a robust immune response towards pathogens while avoiding collateral damage to the host. Several chronic inflammatory disorders are associated with autophagy dysfunction. Pathways that induce autophagy, such as those downstream of pattern recognition receptors, are conversely subject to regulation by autophagy. Autophagy can increase and decrease different components of the same inflammatory signalling cascade in a context-dependent manner. Many immune-related functions of conserved autophagy proteins reflect non-canonical functions of the autophagy machinery, representing new opportunities for therapeutic intervention. This article provides a comprehensive overview of the general functions of autophagy in immunity, the interactions between autophagy and immune signalling pathways and the role of autophagy–immune crosstalk in multicellular immune responses and disease. Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases. Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases. Key Points The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and antigen presentation. Extensive crosstalk between autophagy and inflammatory signalling cascades ensures a robust immune response towards pathogens while avoiding collateral damage to the host. Several chronic inflammatory disorders are associated with autophagy dysfunction. Pathways that induce autophagy, such as those downstream of pattern recognition receptors, are conversely subject to regulation by autophagy. Autophagy can increase and decrease different components of the same inflammatory signalling cascade in a context-dependent manner. Many immune-related functions of conserved autophagy proteins reflect non-canonical functions of the autophagy machinery, representing new opportunities for therapeutic intervention. This article provides a comprehensive overview of the general functions of autophagy in immunity, the interactions between autophagy and immune signalling pathways and the role of autophagy–immune crosstalk in multicellular immune responses and disease. Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful resolution of infection and avoidance of autoimmunity necessitates efficient and timely communication between autophagy and pathways that sense the immune environment. The recent literature indicates that a variety of immune mediators induce or repress autophagy. It is also becoming increasingly clear that immune signalling cascades are subject to regulation by autophagy, and that a return to homeostasis following a robust immune response is critically dependent on this pathway. Importantly, examples of non-canonical forms of autophagy in mediating immunity are pervasive. In this article, the progress in elucidating mechanisms of crosstalk between autophagy and inflammatory signalling cascades is reviewed. Improved mechanistic understanding of the autophagy machinery offers hope for treating infectious and inflammatory diseases.
Audience	Academic
Author	Cadwell, Ken
Author_xml	– sequence: 1 givenname: Ken surname: Cadwell fullname: Cadwell, Ken email: Ken.Cadwell@med.nyu.edu organization: and the Department of Microbiology, Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/27694913$$D View this record in MEDLINE/PubMed
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Snippet	Key Points The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune... Autophagy has broad functions in immunity, ranging from cell-autonomous defence to coordination of complex multicellular immune responses. The successful... Key PointsThe cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune... The cellular degradative process of autophagy participates in multiple aspects of immunity, including cell-autonomous defence, innate immune signalling and...
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SubjectTerms	631/250/2152 631/250/262 631/80/82/39 Adaptive Immunity Amino acids Animals Antigen presentation Autophagosomes - immunology Autophagosomes - metabolism Autophagy Autophagy (Cytology) Autophagy - immunology Bacteria Biomedicine Care and treatment Cellular signal transduction Communicable diseases Cytokines Defense Disease Susceptibility Health aspects Homeostasis Homeostasis - immunology Host-Pathogen Interactions - immunology Humans Immune response Immunity Immunity, Innate Immunology Infections Inflammation - immunology Inflammation - metabolism Inflammatory diseases Observations Pathogens Pattern recognition Pattern recognition receptors Proteins review-article Signal Transduction Tumor necrosis factor-TNF Viruses
Title	Crosstalk between autophagy and inflammatory signalling pathways: balancing defence and homeostasis
URI	https://link.springer.com/article/10.1038/nri.2016.100 https://www.ncbi.nlm.nih.gov/pubmed/27694913 https://www.proquest.com/docview/1833259455 https://www.proquest.com/docview/3143111629 https://www.proquest.com/docview/1835376879 https://www.proquest.com/docview/1837325162 https://pubmed.ncbi.nlm.nih.gov/PMC5343289
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