Complement-Related Regulates Autophagy in Neighboring Cells

Lin, Lin; Rodrigues, Frederico S.L.M.; Kary, Christina; Contet, Alicia; Logan, Mary A.; Baxter, Richard H. G.; Wood, Will; Baehrecke, Eric H.

doi:10.1016/j.cell.2017.06.018

Cited by 53 publications

(50 citation statements)

References 56 publications

(83 reference statements)

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“…Given recent findings about the complement system in D. melanogaster regulating autophagy in neighboring cells, perhaps antimicrobial autophagy responses might even be established in a cell nonautonomous fashion. 47 C. elegans also uses xenophagic elimination of intracellular microbes, and autophagy machinery can be targeted to virulence factors secreted by extracellular microbes invading this organism. The B. thuringiensis Cry5B PFT disrupts host cell membrane integrity and is then endocytosed as part of the host membrane-repair process.…”

Section: Discussionmentioning

confidence: 99%

Autophagy and innate immunity: Insights from invertebrate model organisms

2018

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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. melanogaster. Although C. elegans has no known pattern recognition receptors, this organism has been particularly useful in understanding many aspects of innate immunity. Indeed, work in C. elegans was the first to show xenophagic targeting of microsporidia, a fungal pathogen that infects all animals, and to identify TFEB/HLH-30, a helix-loop-helix transcription factor, as an evolutionarily conserved regulator of autophagy gene expression and host tolerance. Studies in C. elegans have also highlighted the more recently appreciated relationship between autophagy and tolerance to extracellular pathogens. Studies of simple, short-lived invertebrates such as flies and worms will continue to provide valuable insights into the molecular mechanisms by which autophagy and immunity pathways intersect and their contribution to organismal survival. Abbreviations Atg autophagy related BECN1 Beclin 1 CALCOCO2 calcium binding and coiled-coil domain 2 Cry5B crystal toxin 5B Daf abnormal dauer formation DKF-1 D kinase family-1 EPG-7 Ectopic P Granules-7 FuDR fluorodeoxyuridine GFP green fluorescent protein HLH-30 Helix Loop Helix-30 Imd immune deficiency ins-18 INSulin related-18; LET-363, LEThal-363 lgg-1 LC3, GABARAP and GATE-16 family-1 MAPK mitogen-activated protein kinase MATH the meprin and TRAF homology MTOR mechanistic target of rapamycin NBR1 neighbor of BRCA1 gene 1 NFKB nuclear factor of kappa light polypeptide gene enhancer in B cells NOD nucleotide-binding oligomerization domain containing OPTN optineurin PAMPs pathogen-associated molecular patterns Park2 Parkinson disease (autosomal recessive, juvenile) 2, parkin pdr-1 Parkinson disease related PFTs pore-forming toxins PGRP peptidoglycan-recognition proteins PIK3C3 phosphatidylinositol 3- kinase catalytic subunit type 3 pink-1 PINK (PTEN-I induced kinase) homolog PRKD protein kinase D; PLC, phospholipase C PRKN parkin RBR E3 ubiquitin protein ligase PRRs pattern-recognition receptors PtdIns3P phosphatidylinositol-3-phosphate rab-5 RAB family-5 RB1CC1 RB1-inducible coiled-coil 1 RNAi RNA interference sqst SeQueSTosome related SQSTM1 sequestosome 1 TBK1 TANK-binding kinase 1 TFEB transcription factor EB TGFB/TGF-β transforming growth factor beta TLRs toll-like receptors unc-51 UNCoordinated-51 VPS vacuolar protein sorting; VSV, vesicular stomatitis virus VSV-G VSV surface glycoprotein G Wipi2 WD repeat domain, phosphoin...

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Section: Discussionmentioning

confidence: 99%

Autophagy and innate immunity: Insights from invertebrate model organisms

2018

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“…Several studies in Drosophila have identified factors that are specifically necessary for autophagy in the dying salivary gland, but not for survival-associated starvationinduced autophagy in the larval fat body. These include the cell surface engulfment receptor Draper (drpr) (McPhee et al, 2010), its presumed activating ligand, macroglobulin complement-related (mcr) (Lin et al, 2017), and the Ral GTPase and all subunits of its effector, the exocyst complex (Tracy et al, 2016). Whether the role of these factors can be generalized to other systems of ADCD, specifically in mammals, is unknown.…”

Section: Death-specific Autophagy Factorsmentioning

confidence: 99%

Autophagy-dependent cell death – where, how and why a cell eats itself to death

Bialik

Dasari

Kimchi

2018

Journal of Cell Science

237

165

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Autophagy as a means of cell killing was first advanced by Clark's phenotypic description of 'Type II autophagic cell death' in 1990. However, this phenomenon later came into question, because the presence of autophagosomes in dying cells does not necessarily signify that autophagy is the cause of demise, but rather may reflect the efforts of the cell to prevent it. Resolution of this issue comes from a more careful definition of autophagy-dependent cell death (ADCD) as a regulated cell death that is shown experimentally to require different components of the autophagy machinery without involvement of alternative cell death pathways. Following these strict criteria, ADCD has been validated in both lower model organisms and mammalian cells, highlighting its importance for developmental and pathophysiological cell death. Recently, researchers have defined additional morphological criteria that characterize ADCD and begun to explore how the established, well-studied autophagy pathway is subverted from a survival to a death function. This Review explores validated models of ADCD and focuses on the current understanding of the mechanisms by which autophagy can kill a cell.

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“…The expression patterns of Tep1‐4 have been documented by in situ hybridization . The exact function of each Tep in host defense remains poorly understood despite several studies and their potential role as opsonins has not been definitely determined . Although an initial study failed to reveal a role of Tep1 , Tep2 , Tep3 , or Tep4 in several infection models, even when Tep2‐Tep3‐Tep4 triple mutants were assayed , a quadruple Tep1‐Tep2‐Tep3‐Tep4 mutant was reported to be sensitive to some fungal and Gram‐positive bacterial infections, likely because Toll pathway activation is impaired in this quadruple mutant .…”

Section: Introductionmentioning

confidence: 99%

Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization

et al. 2018

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When feeds on, some bacteria cross the intestinal barrier and eventually proliferate in the hemocoel. This process is limited by hemocytes through phagocytosis. requires the quorum-sensing regulator RhlR to elude the cellular immune response of the fly. RhlI synthesizes the autoinducer signal that activates RhlR. Here, we show that mutants are unexpectedly more virulent than mutants, both in fly and in nematode intestinal infection models, suggesting that RhlR has RhlI-independent functions. We also report that RhlR protects from opsonization mediated by the thioester-containing protein 4 (Tep4). mutant bacteria show higher levels of mediated opsonization, as compared to mutants, which prevents lethal bacteremia in the hemocoel. In contrast, in a septic model of infection, in which bacteria are introduced directly into the hemocoel, mutant flies are more resistant to wild-type but not to the mutant. Thus, depending on the infection route, the Tep4 opsonin can either be protective or detrimental to host defense.

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Complement-Related Regulates Autophagy in Neighboring Cells

Cited by 53 publications

References 56 publications

Autophagy and innate immunity: Insights from invertebrate model organisms

Autophagy and innate immunity: Insights from invertebrate model organisms

Autophagy-dependent cell death – where, how and why a cell eats itself to death

Quorum‐sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization

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