Autophagy and innate immunity: Insights from invertebrate model organisms

Cheng-Ju Kuo, Malene Hansen, Emily Troemel

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

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. AbbreviationsAtg autophagy relatedBECN1 Beclin 1CALCOCO2 calcium binding and coiled-coil domain 2Cry5B crystal toxin 5BDaf abnormal dauer formationDKF-1 D kinase family-1EPG-7 Ectopic P Granules-7FuDR fluorodeoxyuridineGFP green fluorescent proteinHLH-30 Helix Loop Helix-30Imd immune deficiencyins-18 INSulin related-18; LET-363, LEThal-363lgg-1 LC3, GABARAP and GATE-16 family-1MAPK mitogen-activated protein kinaseMATH the meprin and TRAF homologyMTOR mechanistic target of rapamycinNBR1 neighbor of BRCA1 gene 1NFKB nuclear factor of kappa light polypeptide gene enhancer in B cellsNOD nucleotide-binding oligomerization domain containingOPTN optineurinPAMPs pathogen-associated molecular patternsPark2 Parkinson disease (autosomal recessive, juvenile) 2, parkinpdr-1 Parkinson disease relatedPFTs pore-forming toxinsPGRP peptidoglycan-recognition proteinsPIK3C3 phosphatidylinositol 3- kinase catalytic subunit type 3pink-1 PINK (PTEN-I induced kinase) homologPRKD protein kinase D; PLC, phospholipase CPRKN parkin RBR E3 ubiquitin protein ligasePRRs pattern-recognition receptorsPtdIns3P phosphatidylinositol-3-phosphaterab-5 RAB family-5RB1CC1 RB1-inducible coiled-coil 1RNAi RNA interferencesqst SeQueSTosome relatedSQSTM1 sequestosome 1TBK1 TANK-binding kinase 1TFEB transcription factor EBTGFB/TGF-β transforming growth factor betaTLRs toll-like receptorsunc-51 UNCoordinated-51VPS vacuolar protein sorting; VSV, vesicular stomatitis virusVSV-G VSV surface glycoprotein GWipi2 WD repeat domain, phosphoinositide interacting 2.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalAutophagy
Volume14
Issue number2
DOIs
Publication statusPublished - 2018 Feb 1

Fingerprint

Autophagy
Invertebrates
Innate Immunity
Caenorhabditis elegans
Pattern Recognition Receptors
Phosphotransferases
Phosphatidylinositols
Drosophila melanogaster
Diptera
Immunity
Transcription Factors
Tiopronin
Phosphatidylinositol 3-Kinase
Microsporidia
BRCA1 Gene
Linear Energy Transfer
Vesicular Stomatitis
Peptidoglycan
Phospholipases
Membrane Glycoproteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Kuo, Cheng-Ju ; Hansen, Malene ; Troemel, Emily. / Autophagy and innate immunity : Insights from invertebrate model organisms. In: Autophagy. 2018 ; Vol. 14, No. 2. pp. 233-242.
@article{290ff7c235cd406898476eda9ba83153,
title = "Autophagy and innate immunity: Insights from invertebrate model organisms",
abstract = "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. AbbreviationsAtg autophagy relatedBECN1 Beclin 1CALCOCO2 calcium binding and coiled-coil domain 2Cry5B crystal toxin 5BDaf abnormal dauer formationDKF-1 D kinase family-1EPG-7 Ectopic P Granules-7FuDR fluorodeoxyuridineGFP green fluorescent proteinHLH-30 Helix Loop Helix-30Imd immune deficiencyins-18 INSulin related-18; LET-363, LEThal-363lgg-1 LC3, GABARAP and GATE-16 family-1MAPK mitogen-activated protein kinaseMATH the meprin and TRAF homologyMTOR mechanistic target of rapamycinNBR1 neighbor of BRCA1 gene 1NFKB nuclear factor of kappa light polypeptide gene enhancer in B cellsNOD nucleotide-binding oligomerization domain containingOPTN optineurinPAMPs pathogen-associated molecular patternsPark2 Parkinson disease (autosomal recessive, juvenile) 2, parkinpdr-1 Parkinson disease relatedPFTs pore-forming toxinsPGRP peptidoglycan-recognition proteinsPIK3C3 phosphatidylinositol 3- kinase catalytic subunit type 3pink-1 PINK (PTEN-I induced kinase) homologPRKD protein kinase D; PLC, phospholipase CPRKN parkin RBR E3 ubiquitin protein ligasePRRs pattern-recognition receptorsPtdIns3P phosphatidylinositol-3-phosphaterab-5 RAB family-5RB1CC1 RB1-inducible coiled-coil 1RNAi RNA interferencesqst SeQueSTosome relatedSQSTM1 sequestosome 1TBK1 TANK-binding kinase 1TFEB transcription factor EBTGFB/TGF-β transforming growth factor betaTLRs toll-like receptorsunc-51 UNCoordinated-51VPS vacuolar protein sorting; VSV, vesicular stomatitis virusVSV-G VSV surface glycoprotein GWipi2 WD repeat domain, phosphoinositide interacting 2.",
author = "Cheng-Ju Kuo and Malene Hansen and Emily Troemel",
year = "2018",
month = "2",
day = "1",
doi = "10.1080/15548627.2017.1389824",
language = "English",
volume = "14",
pages = "233--242",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "2",

}

Autophagy and innate immunity : Insights from invertebrate model organisms. / Kuo, Cheng-Ju; Hansen, Malene; Troemel, Emily.

In: Autophagy, Vol. 14, No. 2, 01.02.2018, p. 233-242.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Autophagy and innate immunity

T2 - Insights from invertebrate model organisms

AU - Kuo, Cheng-Ju

AU - Hansen, Malene

AU - Troemel, Emily

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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. AbbreviationsAtg autophagy relatedBECN1 Beclin 1CALCOCO2 calcium binding and coiled-coil domain 2Cry5B crystal toxin 5BDaf abnormal dauer formationDKF-1 D kinase family-1EPG-7 Ectopic P Granules-7FuDR fluorodeoxyuridineGFP green fluorescent proteinHLH-30 Helix Loop Helix-30Imd immune deficiencyins-18 INSulin related-18; LET-363, LEThal-363lgg-1 LC3, GABARAP and GATE-16 family-1MAPK mitogen-activated protein kinaseMATH the meprin and TRAF homologyMTOR mechanistic target of rapamycinNBR1 neighbor of BRCA1 gene 1NFKB nuclear factor of kappa light polypeptide gene enhancer in B cellsNOD nucleotide-binding oligomerization domain containingOPTN optineurinPAMPs pathogen-associated molecular patternsPark2 Parkinson disease (autosomal recessive, juvenile) 2, parkinpdr-1 Parkinson disease relatedPFTs pore-forming toxinsPGRP peptidoglycan-recognition proteinsPIK3C3 phosphatidylinositol 3- kinase catalytic subunit type 3pink-1 PINK (PTEN-I induced kinase) homologPRKD protein kinase D; PLC, phospholipase CPRKN parkin RBR E3 ubiquitin protein ligasePRRs pattern-recognition receptorsPtdIns3P phosphatidylinositol-3-phosphaterab-5 RAB family-5RB1CC1 RB1-inducible coiled-coil 1RNAi RNA interferencesqst SeQueSTosome relatedSQSTM1 sequestosome 1TBK1 TANK-binding kinase 1TFEB transcription factor EBTGFB/TGF-β transforming growth factor betaTLRs toll-like receptorsunc-51 UNCoordinated-51VPS vacuolar protein sorting; VSV, vesicular stomatitis virusVSV-G VSV surface glycoprotein GWipi2 WD repeat domain, phosphoinositide interacting 2.

AB - 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. AbbreviationsAtg autophagy relatedBECN1 Beclin 1CALCOCO2 calcium binding and coiled-coil domain 2Cry5B crystal toxin 5BDaf abnormal dauer formationDKF-1 D kinase family-1EPG-7 Ectopic P Granules-7FuDR fluorodeoxyuridineGFP green fluorescent proteinHLH-30 Helix Loop Helix-30Imd immune deficiencyins-18 INSulin related-18; LET-363, LEThal-363lgg-1 LC3, GABARAP and GATE-16 family-1MAPK mitogen-activated protein kinaseMATH the meprin and TRAF homologyMTOR mechanistic target of rapamycinNBR1 neighbor of BRCA1 gene 1NFKB nuclear factor of kappa light polypeptide gene enhancer in B cellsNOD nucleotide-binding oligomerization domain containingOPTN optineurinPAMPs pathogen-associated molecular patternsPark2 Parkinson disease (autosomal recessive, juvenile) 2, parkinpdr-1 Parkinson disease relatedPFTs pore-forming toxinsPGRP peptidoglycan-recognition proteinsPIK3C3 phosphatidylinositol 3- kinase catalytic subunit type 3pink-1 PINK (PTEN-I induced kinase) homologPRKD protein kinase D; PLC, phospholipase CPRKN parkin RBR E3 ubiquitin protein ligasePRRs pattern-recognition receptorsPtdIns3P phosphatidylinositol-3-phosphaterab-5 RAB family-5RB1CC1 RB1-inducible coiled-coil 1RNAi RNA interferencesqst SeQueSTosome relatedSQSTM1 sequestosome 1TBK1 TANK-binding kinase 1TFEB transcription factor EBTGFB/TGF-β transforming growth factor betaTLRs toll-like receptorsunc-51 UNCoordinated-51VPS vacuolar protein sorting; VSV, vesicular stomatitis virusVSV-G VSV surface glycoprotein GWipi2 WD repeat domain, phosphoinositide interacting 2.

UR - http://www.scopus.com/inward/record.url?scp=85045249808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045249808&partnerID=8YFLogxK

U2 - 10.1080/15548627.2017.1389824

DO - 10.1080/15548627.2017.1389824

M3 - Review article

C2 - 29130360

AN - SCOPUS:85045249808

VL - 14

SP - 233

EP - 242

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 2

ER -