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Xenophagy

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https://www.readbyqxmd.com/read/29130360/autophagy-and-innate-immunity-insights-from-invertebrate-model-organisms
#1
Cheng-Ju Kuo, Malene Hansen, Emily Troemel
Macroautophagy/autophagy is a fundamental intracellular degradation process with multiple roles in immunity, including direct elimination of intracellular microorganisms via 'xenophagy.' In this review, we summarize studies from the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans that highlight the roles of autophagy in innate immune responses to viral, bacterial, and fungal pathogens. Research from these genetically tractable invertebrates has uncovered several conserved immunological paradigms, such as direct targeting of intracellular pathogens by xenophagy and regulation of autophagy by pattern recognition receptors in D...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29126745/xenophagic-pathways-and-their-bacterial-subversion-in-cellular-self-defense-%C3%AF-%C3%AE-%C3%AE-%C3%AF-%C3%AE-%C3%AF-%C3%AE%C2%B5%C3%AE-everything-is-in-flux
#2
REVIEW
Nadine Radomski, Annica Rebbig, Ralf M Leonhardt, Michael R Knittler
Autophagy is an evolutionarily ancient and highly conserved eukaryotic mechanism that targets cytoplasmic material for degradation. Autophagic flux involves the formation of autophagosomes and their degradation by lysosomes. The process plays a crucial role in maintaining cellular homeostasis and responds to various environmental conditions. While autophagy had previously been thought to be a non-selective process, it is now clear that it can also selectively target cellular organelles, such as mitochondria (referred to as mitophagy) and/or invading pathogens (referred to as xenophagy)...
November 2, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29099277/the-intracellular-microbial-sensor-nlrp4-directs-rho-actin-signaling-to-facilitate-group-a-streptococcus-containing-autophagosome-like-vacuole-formation
#3
Takashi Nozawa, Chihiro Aikawa, Atsuko Minowa-Nozawa, Ichiro Nakagawa
Xenophagy, also known as antibacterial autophagy, functions as a crucial defense system that can utilize intracellular pattern recognition sensors, such as NLRP4, to recognize and selectively eliminate bacterial pathogens. However, little is known about how NLRP4 regulates xenophagy. Here, we report that NLRP4 binds ARHGDIA (Rho GDP dissociation inhibitor α) to regulate Rho GTPase signaling and facilitate actin-mediated xenophagy. Specifically, NLRP4 is recruited to Group A Streptococcus (GAS) and colocalizes with GAS-containing autophagosome-like vacuoles (GcAVs), where it regulates ARHGDIA-Rho GTPase recruitment to promote autophagosome formation...
November 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28965939/impaired-intracellular-pathogen-clearance-and-inflammatory-joint-disease-is-whipple-s-disease-a-guiding-light
#4
Jean-Marie Berthelot, Xavier Puéchal
Whipple's disease can mimic spondyloarthritis (SpA) or rheumatoid arthritis (RA) for many years and, in a few cases, induces the development of antibodies to cyclic citrullinated peptides. The causative agent Tropheryma whipplei can smolder within cells, including macrophages, by suppressing the xenophagic process, a type of selective autophagy that targets pathogens. Other inflammatory joint diseases may also stem from impaired xenophagy with persistence of bacteria or viruses that can eventually migrate from the mucous membranes to the joints and entheses, where they may exert adverse effects on immune responses, even if they fail to replicate...
September 28, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28960115/nbr1-mediated-antiviral-xenophagy-in-plant-immunity
#5
Anders Hafrén, Daniel Hofius
Macroautophagy/autophagy intersects with metazoan virus infections in highly complex and multifaceted ways. Autophagy mechanisms are part of antiviral immunity, but can be manipulated by several viruses to the benefit of infection. In plants, however, the roles of autophagy in virus infections have only recently started to emerge. Here, we present and discuss our recent study that identified 2 prominent functions of autophagy upon cauliflower mosaic virus (CaMV) infection in Arabidopsis. We found that "bulk" autophagy significantly extended the life span of infected plants and increased total virus production...
September 29, 2017: Autophagy
https://www.readbyqxmd.com/read/28806134/ilir-viral-a-web-resource-for-lir-motif-containing-proteins-in-viruses
#6
Anne-Claire Jacomin, Siva Samavedam, Hannah Charles, Ioannis P Nezis
Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins...
October 3, 2017: Autophagy
https://www.readbyqxmd.com/read/28799902/innate-immunity-to-intracellular-pathogens-balancing-microbial-elimination-and-inflammation
#7
REVIEW
Gabriel Mitchell, Ralph R Isberg
Recent excitement regarding immune clearance of intracellular microorganisms has focused on two systems that maintain cellular homeostasis. One system includes cellular autophagy components that mediate degradation of pathogens in membrane-bound compartments, in a process termed xenophagy. The second system is driven by interferon-regulated GTPases that promote rupture of pathogen-containing vacuoles and microbial degradation. In the case of xenophagy, pathogen sequestration and compartmentalization suppress inflammation...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28685931/structure-of-the-wd40-domain-of-human-atg16l1
#8
Milica Bajagic, Archna Archna, Petra Büsing, Andrea Scrima
Autophagy-related protein ATG16L1 is a component of the mammalian ATG12∼ATG5/ATG16L1 complex, which acts as E3-ligase to catalyze lipidation of LC3 during autophagosome biogenesis. The N-terminal part of ATG16L1 comprises the ATG5-binding site and coiled-coil dimerization domain, both also present in yeast ATG16 and essential for bulk and starvation induced autophagy. While absent in yeast ATG16, mammalian ATG16L1 further contains a predicted C-terminal WD40-domain, which has been shown to be involved in mediating interaction with diverse factors in the context of alternative functions of autophagy, such as inflammatory control and xenophagy...
September 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28683091/endothelial-cells-are-intrinsically-defective-in-xenophagy-of-streptococcus-pyogenes
#9
Shiou-Ling Lu, Tsuyoshi Kawabata, Yi-Lin Cheng, Hiroko Omori, Maho Hamasaki, Tatsuya Kusaba, Ryo Iwamoto, Hirokazu Arimoto, Takeshi Noda, Yee-Shin Lin, Tamotsu Yoshimori
Group A Streptococcus (GAS) is deleterious pathogenic bacteria whose interaction with blood vessels leads to life-threatening bacteremia. Although xenophagy, a special form of autophagy, eliminates invading GAS in epithelial cells, we found that GAS could survive and multiply in endothelial cells. Endothelial cells were competent in starvation-induced autophagy, but failed to form double-membrane structures surrounding GAS, an essential step in xenophagy. This deficiency stemmed from reduced recruitment of ubiquitin and several core autophagy proteins in endothelial cells, as demonstrated by the fact that it could be rescued by exogenous coating of GAS with ubiquitin...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#10
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28481361/linear-ubiquitination-of-cytosolic-salmonella-typhimurium-activates-nf-%C3%AE%C2%BAb-and-restricts-bacterial-proliferation
#11
Sjoerd J L van Wijk, Franziska Fricke, Lina Herhaus, Jalaj Gupta, Katharina Hötte, Francesco Pampaloni, Paolo Grumati, Manuel Kaulich, Yu-Shin Sou, Masaaki Komatsu, Florian R Greten, Simone Fulda, Mike Heilemann, Ivan Dikic
Ubiquitination of invading Salmonella Typhimurium triggers autophagy of cytosolic bacteria and restricts their spread in epithelial cells. Ubiquitin (Ub) chains recruit autophagy receptors such as p62/SQSTM1, NDP52/CALCOCO and optineurin (OPTN), which initiate the formation of double-membrane autophagosomal structures and lysosomal destruction in a process known as xenophagy. Besides this, the functional consequences and mechanistic regulation of differentially linked Ub chains at the host-Salmonella interface have remained unexplored...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28481331/lubac-synthesized-linear-ubiquitin-chains-restrict-cytosol-invading-bacteria-by-activating-autophagy-and-nf-%C3%AE%C2%BAb
#12
Jessica Noad, Alexander von der Malsburg, Claudio Pathe, Martin A Michel, David Komander, Felix Randow
Cell-autonomous immunity relies on the ubiquitin coat surrounding cytosol-invading bacteria functioning as an 'eat-me' signal for xenophagy. The origin, composition and precise mode of action of the ubiquitin coat remain incompletely understood. Here, by studying Salmonella Typhimurium, we show that the E3 ligase LUBAC generates linear (M1-linked) polyubiquitin patches in the ubiquitin coat, which serve as antibacterial and pro-inflammatory signalling platforms. LUBAC is recruited via its subunit HOIP to bacterial surfaces that are no longer shielded by host membranes and are already displaying ubiquitin, suggesting that LUBAC amplifies and refashions the ubiquitin coat...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28456980/lysophagy-a-method-for-monitoring-lysosomal-rupture-followed-by-autophagy-dependent-recovery
#13
Takanobu Otomo, Tamotsu Yoshimori
Selective autophagy recognizes specific targets, including damaged mitochondria (mitophagy), aggregated proteins (aggrephagy), and invading bacteria (xenophagy) to engulf by isolation membrane, and degrades toxic materials within lysosomes. We recently revealed that a membrane-damaged lysosome itself also becomes a target of autophagy and named this process lysophagy. In this chapter, we describe methods for monitoring lysophagy; detecting lysosomal damage by staining of galectin and study the subsequent autophagic process in cultured mammalian cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28367819/-autophagy-atg-proteins-and-infectious-diseases
#14
REVIEW
Isabelle Vergne, Frank Lafont, Lucile Espert, Audrey Esclatine, Martine Biard-Piechaczyk
One of the main functions of the autophagy pathway is to control infections. Intracellular micro-organisms or their products once internalized in the host cell can be directly degraded by autophagy, a process called xenophagy. Autophagy is also involved in other innate immune responses and participates to the adaptive immune system. In addition, several autophagy proteins play a role in the development of infectious diseases independently of their role in the autophagy pathway. To replicate efficiently, pathogens have therefore evolved to counteract this process or to exploit it to their own profit...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28213625/8-nitro-cgmp-a-novel-protein-reactive-cnmp-and-its-emerging-roles-in-autophagy
#15
REVIEW
Hirokazu Arimoto, Daiki Takahashi
Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO2) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs...
2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28028054/fluorescence-based-atg8-sensors-monitor-localization-and-function-of-lc3-gabarap-proteins
#16
Alexandra Stolz, Mateusz Putyrski, Ivana Kutle, Jessica Huber, Chunxin Wang, Viktória Major, Sachdev S Sidhu, Richard J Youle, Vladimir V Rogov, Volker Dötsch, Andreas Ernst, Ivan Dikic
Autophagy is a cellular surveillance pathway that balances metabolic and energy resources and transports specific cargos, including damaged mitochondria, other broken organelles, or pathogens for degradation to the lysosome. Central components of autophagosomal biogenesis are six members of the LC3 and GABARAP family of ubiquitin-like proteins (mATG8s). We used phage display to isolate peptides that possess bona fide LIR (LC3-interacting region) properties and are selective for individual mATG8 isoforms. Sensitivity of the developed sensors was optimized by multiplication, charge distribution, and fusion with a membrane recruitment (FYVE) or an oligomerization (PB1) domain...
February 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28026986/xenophagy-a-battlefield-between-host-and-microbe-and-a-possible-avenue-for-cancer-treatment
#17
Kai Mao, Daniel J Klionsky
In eukaryotes, xenophagy is defined as a type of selective macroautophagy/autophagy that is used for eliminating invading pathogens. In contrast to other types of selective autophagy, such as mitophagy, pexophagy and ribophagy, xenophagy is used by eukaryotes for targeting microbes-hence the prefix "xeno" meaning "other" or "foreign"-that have infected a host cell, leading to their lysosomal degradation. This unique characteristic links xenophagy to antibacterial and antiviral defenses, as well as the immune response...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27924676/bacterial-xenophagy-and-its-possible-role-in-cancer-a-potential-antimicrobial-strategy-for-cancer-prevention-and-treatment
#18
Xinbing Sui, Xiao Liang, Liuxi Chen, Chunming Guo, Weidong Han, Hongming Pan, Xue Li
Macroautophagy/autophagy is a conserved catabolic process through which cellular excessive or dysfunctional proteins and organelles are transported to the lysosome for terminal degradation and recycling. Over the past few years increasing evidence has suggested that autophagy is not only a simple metabolite recycling mechanism, but also plays a critical role in the removal of intracellular pathogens such as bacteria and viruses. When autophagy engulfs intracellular pathogens, the pathway is called 'xenophagy' because it leads to the elimination of foreign microbes...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27906974/in-silico-knockout-studies-of-xenophagic-capturing-of-salmonella
#19
Jennifer Scheidel, Leonie Amstein, Jörg Ackermann, Ivan Dikic, Ina Koch
The degradation of cytosol-invading pathogens by autophagy, a process known as xenophagy, is an important mechanism of the innate immune system. Inside the host, Salmonella Typhimurium invades epithelial cells and resides within a specialized intracellular compartment, the Salmonella-containing vacuole. A fraction of these bacteria does not persist inside the vacuole and enters the host cytosol. Salmonella Typhimurium that invades the host cytosol becomes a target of the autophagy machinery for degradation...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27880896/rnf166-determines-recruitment-of-adaptor-proteins-during-antibacterial-autophagy
#20
Robert J Heath, Gautam Goel, Leigh A Baxt, Jason S Rush, Vishnu Mohanan, Geraldine L C Paulus, Vijay Jani, Kara G Lassen, Ramnik J Xavier
Xenophagy is a form of selective autophagy that involves the targeting and elimination of intracellular pathogens through several recognition, recruitment, and ubiquitination events. E3 ubiquitin ligases control substrate selectivity in the ubiquitination cascade; however, systematic approaches to map the role of E3 ligases in antibacterial autophagy have been lacking. We screened more than 600 putative human E3 ligases, identifying E3 ligases that are required for adaptor protein recruitment and LC3-bacteria colocalization, critical steps in antibacterial autophagy...
November 22, 2016: Cell Reports
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