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. 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...

Immune profiles of male giant panda (Ailuropoda melanoleuca) during breeding season

“…Autophagy is a fundamental intracellular bulk degradation process with multiple roles in innate immune responses and cellular stress [31,32]. Beclin1 and LC3 encoded by BECN1, GABARAPL1, respectively, were both up-regulated.…”

The Role of Autophagy and Autophagy Receptor NDP52 in Microbial Infections

“…In innate immunity, autophagy contributes to the pattern response downstream of the effector receptor, which in turn promotes phagocytosis [17]. Autophagy and Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) have mutual regulation [18,19]. For example, different TLRs (including TLR-1, TLR-2, TLR-3, TLR-5, and TLR-6) are activated by their ligands to promote autophagy by interacting with Beclin1 via Myd88 or Trif [20], thus contributing to the clearance of pathogenic microorganisms and enhancing the protective effect of the host [21].…”

Conserved gene reactivity revealed in cnidarian innate immunity during zoonotic infection

“…Although studies of traditional model systems such as the mouse, fruit fly and roundworm have provided a wealth of information on the molecular basis of immunity in humans (Kuo et al 2018), our knowledge is currently improving dramatically thanks to studies conducted on less conventional species from other taxa such as Amphioxus (Zhang et al 2018), and Hydra (Bosch 2013). Corals, for example, can have up to 10% of their genes matching human's but not those of the fruit fly or roundworm models (Kortschak et al 2003).…”