Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.
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Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing NFκB activity through A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of A20, an NFκB inhibitor, in F4/80(hi) macrophages in the spleen, peritoneum and kidney. We show that p62, an autophagic adaptor protein, captures A20 to sequester it in the autophagosome. This allows the macrophages to release chemokines to recruit neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher susceptibility to Candida albicans infection due to impairment in neutrophil recruitment. Thus, at least in the specific aforementioned tissues, autophagy appears to break A20-dependent suppression in F4/80(hi) macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.
Autophagy-Related Protein 7
Intracellular Signaling Peptides and Proteins
Mice, Inbred C57BL
NF-kappa B p50 Subunit
Tumor Necrosis Factor alpha-Induced Protein 3
Published Version (Please cite this version)10.1038/ncomms6779
Publication InfoDanzaki, K; Hammer, Gianna; He, YW; Inoue, M; Kanayama, M; & Shinohara, Mari L (2015). Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity. Nat Commun, 6. pp. 5779. 10.1038/ncomms6779. Retrieved from https://hdl.handle.net/10161/9376.
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Assistant Professor of Immunology
The study of microbial communities that reside on and within the human body (the microbiome) is considered one of the hottest areas of science today. It is now well appreciated that the microbiome has remarkable influence on diverse aspects of human health and disease. To understand how the microbiome exerts such influence, our lab seeks to define the mechanisms by which cells of the immune system interact with microbes that reside in the intestine. To the immune system, co-existence with mic
Associate Professor of Immunology
We need to mount a strong immune response against pathogens during infections, but excessive and uncontrolled immune reactions can lead to autoimmunity. How does our immune system keep the balance fine-tuned? This is a central question being asked in my laboratory.Immune system needs to detect pathogens quickly and effectively. This is performed by the innate immune system, which includes cells such as macrophages and dendritic cells (DCs). Pathogens are recog
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