Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.
Abstract
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.
Type
Journal articleSubject
AnimalsAutophagy
Autophagy-Related Protein 7
Candida albicans
Candidiasis
Chemokine CXCL1
Chemokine CXCL2
Chemokines
Chemotaxis
Cysteine Endopeptidases
Down-Regulation
Female
Immunity, Innate
Inflammation
Intracellular Signaling Peptides and Proteins
Kidney
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Microtubule-Associated Proteins
Myeloid Cells
NF-kappa B p50 Subunit
Neutrophils
Peritoneum
Signal Transduction
Spleen
Tumor Necrosis Factor alpha-Induced Protein 3
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https://hdl.handle.net/10161/9376Published Version (Please cite this version)
10.1038/ncomms6779Publication Info
Kanayama, M; Inoue, M; Danzaki, K; Hammer, G; He, Y; & Shinohara, ML (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Gianna Hammer
Adjunct 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
You-Wen He
Professor of Immunology
We study T cell biology in health and disease. Our current study is divided into two
parts. Part I is to investigate T lymphocyte-mediated anti-caner immunity. We have
found that host complement inhibits the cytokine IL-10 production in CD8+ tumor infiltrating
lymphocytes through complement receptors C3aR and C5aR. Complement-deficient animals
are resistant to tumor development in a T cell- and IL-10-dependent manner. CD8+ tumor
infiltrating T cells express IL-10 when compl
Mari L. Shinohara
Associate Professor of Immunology
Shinohara Lab WebsiteImmune responses against pathogens are essential for host protection,
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.
The immune system needs to detect pathogens quickly and effectively. This is performed
by the innate immune system, which includes cells such as mac
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