Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila
Abstract
:1. Drosophila melanogaster: A Case Study of the Innate Immune System
1.1. Introduction
1.2. Drosophila: An Ever-Relevant Model
2. Overview of the NF-κB Signaling Pathways in Drosophila
2.1. The IMD Pathway
2.2. The Toll Pathway
2.3. Regarding Both Pathways
3. From PAMP Sensing to NF-κB Relish Activity
3.1. PGRP-LC/PGRP-LE-IMD Signaling Complex
3.2. From IMD to Relish Activation
3.3. Molecular Mechanism of Relish Activation
3.4. Complex of Transcription Factors
3.5. Other Ways to Activate NF-κB Relish Pathway
4. Various Ways to Inactivate the NF-κB IMD-Relish Pathway
4.1. At the Level of the Receptor
4.2. At the Level of the Signaling Cascade
4.3. At the Level of Relish
4.4. IMD Pathway Modulation: A Highly Dynamic Process
5. Regulation of NF-κB Relish Target Genes Expression
5.1. First Discovery of Akirin in Innate Immunity
5.2. Akirin Fine-Tune the NF-κB Response in Drosophila and Mammals
5.3. Mechanism of NF-κB Selective Response
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
- Dzik, J.M. The ancestry and cumulative evolution of immune reactions. Acta Biochim. Pol. 2010, 57, 443–466. [Google Scholar] [CrossRef] [PubMed]
- Janeway, C.A.; Medzhitov, R. Innate Immune Recognition. Annu. Rev. Immunol. 2002, 20, 197–216. [Google Scholar] [CrossRef] [PubMed]
- Medzhitov, R. Origin and physiological roles of inflammation. Nature 2008, 454, 428–435. [Google Scholar] [CrossRef]
- Nathan, C. Points of control in inflammation. Nature 2002, 420, 846–852. [Google Scholar] [CrossRef] [PubMed]
- Karin, M.; Lawrence, T.; Nizet, V. Innate Immunity Gone Awry: Linking Microbial Infections to Chronic Inflammation and Cancer. Cell 2006, 124, 823–835. [Google Scholar] [CrossRef]
- Maeda, S.; Omata, M. Inflammation and cancer: Role of nuclear factor-kappaB activation. Cancer Sci. 2008, 99, 836–842. [Google Scholar] [CrossRef]
- Hoffmann, J.A.; Reichhart, J.-M. Drosophila innate immunity: An evolutionary perspective. Nat. Immunol. 2002, 3, 121–126. [Google Scholar] [CrossRef]
- Leulier, F.; Lemaitre, B. Toll-like receptors—Taking an evolutionary approach. Nat. Rev. Genet. 2008, 9, 165–178. [Google Scholar] [CrossRef]
- Gonzalez, C. Drosophila melanogaster: A model and a tool to investigate malignancy and identify new therapeutics. Nat. Rev. Cancer 2013, 13, 172–183. [Google Scholar] [CrossRef]
- Villegas, S.N. One hundred years of Drosophila cancer research: No longer in solitude. Dis. Models Mech. 2019, 12, dmm039032. [Google Scholar] [CrossRef] [Green Version]
- Sonoshita, M.; Cagan, R.L. Modeling human cancers in Drosophila. In Current Topics in Developmental Biology; Pick, L., Ed.; Academic Press: Cambridge, MA, USA, 2017; pp. 287–309. [Google Scholar]
- Enomoto, M.; Siow, C.; Igaki, T. Drosophila as a cancer model. In Drosophila Models for Human Diseases; Yamaguchi, M., Ed.; Springer: Singapore, 2018; pp. 173–194. [Google Scholar]
- Brumby, A.M.; Richardson, H.E. Using Drosophila melanogaster to map human cancer pathways. Nat. Rev. Cancer 2005, 5, 626–639. [Google Scholar] [CrossRef] [PubMed]
- Parvy, J.-P.; Hodgson, J.A.; Cordero, J.B. Drosophila as a Model System to Study Nonautonomous Mechanisms Affecting Tumour Growth and Cell Death. Bio. Med Res. Int. 2018, 2018, 7152962. [Google Scholar]
- Gong, S.; Zhang, Y.; Tian, A.; Deng, W.-M. Tumor models in various Drosophila tissues. WIREs Mech. Dis. 2021, 13, e1525. [Google Scholar] [CrossRef] [PubMed]
- Williams, M.J. Drosophila Hemopoiesis and Cellular Immunity. J. Immunol. 2007, 178, 4711. [Google Scholar] [CrossRef]
- Leclerc, V.; Reichhart, J.-M. The immune response of Drosophila melanogaster. Immunol. Rev. 2004, 198, 59–71. [Google Scholar] [CrossRef]
- Imler, J.-L. Overview of Drosophila immunity: A historical perspective. Dev. Comp. Immunol. 2014, 42, 3–15. [Google Scholar] [CrossRef]
- Volchenkov, R.; Sprater, F.; Vogelsang, P.; Appel, S. The 2011 Nobel Prize in Physiology or Medicine. Scand. J. Immunol. 2012, 75, 1–4. [Google Scholar] [CrossRef]
- Sen, R.; Baltimore, D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986, 46, 705–716. [Google Scholar] [CrossRef]
- Hetru, C.; Hoffmann, J.A. NF-κB in the Immune Response of Drosophila. Cold Spring Harb. Perspect. Biol. 2009, 1, a000232. [Google Scholar] [CrossRef]
- Neyen, C.; Poidevin, M.; Roussel, A.; Lemaitre, B. Tissue- and Ligand-Specific Sensing of Gram-Negative Infection in Drosophila by PGRP-LC Isoforms and PGRP-LE. J. Immunol. 2012, 189, 1886. [Google Scholar] [CrossRef]
- Werner, T.; Liu, G.; Kang, D.; Ekengren, S.; Steiner, H.; Hultmark, D. A family of peptidoglycan recognition proteins in the fruit fly Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 2000, 97, 13772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, R.; Silverman, N.; Hong, M.; Liao, D.S.; Chung, Y.; Chen, Z.J.; Maniatis, T. The Role of Ubiquitination in Drosophila Innate Immunity. J. Biol. Chem. 2005, 280, 34048–34055. [Google Scholar] [CrossRef] [PubMed]
- Kleino, A.; Valanne, S.; Ulvila, J.; Kallio, J.; Myllymäki, H.; Enwald, H.; Stöven, S.; Poidevin, M.; Ueda, R.; Hultmark, D.; et al. Inhibitor of apoptosis 2 and TAK1 binding protein are components of the Drosophila Imd pathway. EMBO J. 2005, 24, 3423. [Google Scholar] [CrossRef] [PubMed]
- Mulero, M.C.; Huxford, T.; Ghosh, G. NF-κB, IκB, and IKK: Integral Components of Immune System Signaling. Adv. Exp. Med. Biol. 2019, 1172, 207–226. [Google Scholar] [PubMed]
- Silverman, N.; Zhou, R.; Erlich, R.L.; Hunter, M.; Bernstein, E.; Schneider, D.; Maniatis, T. Immune Activation of NF-κB and JNK Requires Drosophila TAK1. J. Biol. Chem. 2003, 278, 48928–48934. [Google Scholar] [CrossRef] [PubMed]
- Vidal, S.; Khush, R.S.; Leulier, F.; Tzou, P.; Nakamura, M.; Lemaitre, B. Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-κB-dependent innate immune responses. Genes Dev. 2001, 15, 1900–1912. [Google Scholar] [CrossRef]
- Ertürk-Hasdemir, D.; Broemer, M.; Leulier, F.; Lane, W.S.; Paquette, N.; Hwang, D.; Kim, C.-H.; Stöven, S.; Meier, P.; Silverman, N. Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes. Proc. Natl. Acad. Sci. USA 2009, 106, 9779. [Google Scholar] [CrossRef]
- Gilmore, T.D. Introduction to NF-κB: Players, pathways, perspectives. Oncogene 2006, 25, 6680. [Google Scholar] [CrossRef]
- Levy, F.; Rabel, D.; Charlet, M.; Bulet, P.; Hoffmann, J.A.; Ehret-Sabatier, L. Peptidomic and proteomic analyses of the systemic immune response of Drosophila. Biochimie 2004, 86, 607–616. [Google Scholar] [CrossRef]
- Myllymäki, H.; Valanne, S.; Rämet, M. The Drosophila Imd Signaling Pathway. J. Immunol. 2014, 192, 3455. [Google Scholar] [CrossRef]
- Ferrandon, D.; Imler, J.-L.; Hetru, C.; Hoffmann, J.A. The Drosophila systemic immune response: Sensing and signalling during bacterial and fungal infections. Nat. Rev. Immunol. 2007, 7, 862. [Google Scholar] [CrossRef] [PubMed]
- Toke, O. Antimicrobial peptides: New candidates in the fight against bacterial infections. Pept. Sci. 2005, 80, 717–735. [Google Scholar] [CrossRef] [PubMed]
- Guo, L.; Karpac, J.; Tran, S.L.; Jasper, H. PGRP-SC2 Promotes Gut Immune Homeostasis to Limit Commensal Dysbiosis and Extend Lifespan. Cell 2014, 156, 109–122. [Google Scholar] [CrossRef] [PubMed]
- Lhocine, N.; Ribeiro, P.S.; Buchon, N.; Wepf, A.; Wilson, R.; Tenev, T.; Lemaitre, B.; Gstaiger, M.; Meier, P.; Leulier, F. PIMS Modulates Immune Tolerance by Negatively Regulating Drosophila Innate Immune Signaling. Cell Host Microbe 2008, 4, 147–158. [Google Scholar] [CrossRef] [PubMed]
- Maillet, F.; Bischoff, V.; Vignal, C.; Hoffmann, J.; Royet, J. The Drosophila Peptidogly can Recognition Protein PGRP-LF Blocks PGRP-LC and IMD/JNK Pathway Activation. Cell Host Microbe 2008, 3, 293–303. [Google Scholar] [CrossRef] [PubMed]
- Paredes, J.C.; Welchman, D.P.; Poidevin, M.; Lemaitre, B. Negative Regulation by Amidase PGRPs Shapes the Drosophila Antibacterial Response and Protects the Fly from Innocuous Infection. Immunity 2011, 35, 770–779. [Google Scholar] [CrossRef] [PubMed]
- Morris, O.; Liu, X.; Domingues, C.; Runchel, C.; Chai, A.; Basith, S.; Tenev, T.; Chen, H.; Choi, S.; Pennetta, G.; et al. Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense. Cell Host Microbe 2016, 20, 283–295. [Google Scholar] [CrossRef]
- Lemaitre, B.; Nicolas, E.; Michaut, L.; Reichhart, J.-M.; Hoffmann, J.A. The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults. Cell 1996, 86, 973–983. [Google Scholar] [CrossRef]
- Chamy, L.E.; Leclerc, V.; Caldelari, I.; Reichhart, J.-M. Sensing of “danger signals” and pathogen-associated molecular patterns defines binary signaling pathways “upstream” of Toll. Nat. Immunol. 2008, 9, 1165. [Google Scholar] [CrossRef]
- Gottar, M.; Gobert, V.; Matskevich, A.A.; Reichhart, J.-M.; Wang, C.; Butt, T.M.; Belvin, M.; Hoffmann, J.A.; Ferrandon, D. Dual Detection of Fungal Infections in Drosophila via Recognition of Glucans and Sensing of Virulence Factors. Cell 2006, 127, 1425–1437. [Google Scholar] [CrossRef]
- Issa, N.; Guillaumot, N.; Lauret, E.; Matt, N.; Schaeffer-Reiss, C.; Van Dorsselaer, A.; Reichhart, J.-M.; Veillard, F. The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway. Mol. Cell 2018, 69, 539–550. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, H.-R.; Chen, Z.J.; Kunes, S.; Chang, G.-D.; Maniatis, T. Endocytic pathway is required for Drosophila Toll innate immune signaling. Proc. Natl. Acad. Sci. USA 2010, 107, 8322–8327. [Google Scholar] [CrossRef] [PubMed]
- Horng, T.; Medzhitov, R. Drosophila MyD88 is an adapter in the Toll signaling pathway. Proc. Natl. Acad. Sci. USA 2001, 98, 12654. [Google Scholar] [CrossRef]
- Sun, H.; Bristow, B.N.; Qu, G.; Wasserman, S.A. A heterotrimeric death domain complex in Toll signaling. Proc. Natl. Acad. Sci. USA 2002, 99, 12871. [Google Scholar] [CrossRef] [PubMed]
- Tauszig-Delamasure, S.; Bilak, H.; Capovilla, M.; Hoffmann, J.A.; Imler, J.-L. Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat. Immunol. 2001, 3, 91. [Google Scholar] [CrossRef]
- Xiao, T.; Towb, P.; Wasserman, S.A.; Sprang, S.R. Three-Dimensional Structure of a Complex between the Death Domains of Pelle and Tube. Cell 1999, 99, 545–555. [Google Scholar] [CrossRef]
- Moncrieffe, M.C.; Grossmann, J.G.; Gay, N.J. Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling. J. Biol. Chem. 2008, 283, 33447–33454. [Google Scholar] [CrossRef]
- Wu, L.P.; Anderson, K.V. Regulated nuclear import of Rel proteins in the Drosophila immune response. Nature 1998, 392, 93. [Google Scholar] [CrossRef]
- Daigneault, J.; Klemetsaune, L.; Wasserman, S.A. The IRAK homolog Pelle is the functional counterpart of IκB kinase in the Drosophila Toll pathway. PLoS ONE 2013, 8, e75150. [Google Scholar] [CrossRef]
- Roth, S.; Stein, D.; Nüsslein-Volhard, C. A gradient of nuclear localization of the dorsal protein determines dorsoventral pattern in the Drosophila embryo. Cell 1989, 59, 1189–1202. [Google Scholar] [CrossRef]
- Rushlow, C.A.; Han, K.; Manley, J.L.; Levine, M. The graded distribution of the dorsal morphogen is initiated by selective nuclear transport in Drosophila. Cell 1989, 59, 1165–1177. [Google Scholar] [CrossRef]
- Steward, R. Relocalization of the dorsal protein from the cytoplasm to the nucleus correlates with its function. Cell 1989, 59, 1179–1188. [Google Scholar] [CrossRef]
- Imler, J.-L.; Hoffmann, J.A. Toll receptors in innate immunity. Trends Cell Biol. 2001, 11, 304–311. [Google Scholar] [CrossRef]
- De Gregorio, E.; Han, S.-J.; Lee, W.-J.; Baek, M.-J.; Osaki, T.; Kawabata, S.-I.; Lee, B.-L.; Iwanaga, S.; Lemaitre, B.; Brey, P.T. An Immune-Responsive Serpin Regulates the Melanization Cascade in Drosophila. Dev. Cell 2002, 3, 581–592. [Google Scholar] [CrossRef]
- Valanne, S.; Wang, J.-H.; Rämet, M. The Drosophila Toll Signaling Pathway. J. Immunol. 2011, 186, 649. [Google Scholar] [CrossRef]
- Tanji, T.; Yun, E.-Y.; Ip, Y.T. Heterodimers of NF-κB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proc. Natl. Acad. Sci. USA 2010, 107, 14715. [Google Scholar] [CrossRef]
- Ji, S.; Sun, M.; Zheng, X.; Li, L.; Sun, L.; Chen, D.; Sun, Q. Cell-surface localization of Pellino antagonizes Toll-mediated innate immune signalling by controlling MyD88 turnover in Drosophila. Nat. Commun. 2014, 5, 3458. [Google Scholar] [CrossRef]
- Haghayeghi, A.; Sarac, A.; Czerniecki, S.; Grosshans, J.; Schöck, F. Pellino enhances innate immunity in Drosophila. Mech. Dev. 2010, 127, 301–307. [Google Scholar] [CrossRef]
- Kleino, A.; Silverman, N. Regulation of the Drosophila Imd pathway by signaling amyloids. Insect Biochem. Mol. Biol. 2019, 108, 16–23. [Google Scholar] [CrossRef]
- Kleino, A.; Ramia, N.F.; Bozkurt, G.; Shen, Y.; Nailwal, H.; Huang, J.; Napetschnig, J.; Gangloff, M.; Chan, F.K.; Wu, H.; et al. Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of the Adaptor Protein Imd to Initiate Drosophila NF-κB Signaling. Immunity 2017, 47, 635–647. [Google Scholar] [CrossRef]
- Chen, L.; Paquette, N.; Mamoor, S.; Rus, F.; Nandy, A.; Leszyk, J.; Shaffer, S.A.; Silverman, N. Innate immune signaling in Drosophila is regulated by transforming growth factor β (TGFβ)-activated kinase (Tak1)-triggered ubiquitin editing. J. Biol. Chem. 2017, 292, 8738–8749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baltimore, D. NF-κB is 25. Nat. Immunol. 2011, 12, 683–685. [Google Scholar] [CrossRef] [PubMed]
- Rus, F.; Flatt, T.; Tong, M.; Aggarwal, K.; Okuda, K.; Kleino, A.; Yates, E.; Tatar, M.; Silverman, N. Ecdysone triggered PGRP-LC expression controls Drosophila innate immunity. EMBO J. 2013, 32, 1626–1638. [Google Scholar] [CrossRef] [PubMed]
- Verma, P.; Tapadia, M.G. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster. Mol. Immunol. 2015, 66, 325–339. [Google Scholar] [CrossRef] [PubMed]
- Barretto, E.C.; Polan, D.M.; Beevor-Potts, A.N.; Lee, B.; Grewal, S.S. Tolerance to Hypoxia Is Promoted by FOXO Regulation of the Innate Immunity Transcription Factor NF-κB/Relish in Drosophila. Genetics 2020, 215, 1013–1025. [Google Scholar] [CrossRef]
- Goto, A.; Okado, K.; Martins, N.; Cai, H.; Barbier, V.; Lamiable, O.; Troxler, L.; Santiago, E.; Kuhn, L.; Paik, D.; et al. The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila. Immunity 2018, 49, 225–234. [Google Scholar] [CrossRef]
- Cai, H.; Holleufer, A.; Simonsen, B.; Schneider, J.; Lemoine, A.; Gad, H.H.; Huang, J.X.; Huang, J.Q.; Chen, D.; Peng, T.; et al. 2′3′-cGAMP triggers a STING- and NF-κB–dependent broad antiviral response in Drosophila. Sci. Signal 2020, 13, eabc4537. [Google Scholar] [CrossRef]
- Chen, D.; Roychowdhury-Sinha, A.; Prakash, P.; Lan, X.; Fan, W.; Goto, A.; Hoffmann, J.A. A time course transcriptomic analysis of host and injected oncogenic cells reveals new aspects of Drosophila immune defenses. Proc. Natl. Acad. Sci. USA 2021, 118, e2100825118. [Google Scholar] [CrossRef]
- Charroux, B.; Capo, F.; Kurz, C.L.; Peslier, S.; Chaduli, D.; Viallat-lieutaud, A.; Royet, J. Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota. Cell Host Microbe 2018, 23, 215–228. [Google Scholar] [CrossRef]
- Zaidman-Rémy, A.; Poidevin, M.; Hervé, M.; Welchman, D.P.; Paredes, J.C.; Fahlander, C.; Steiner, H.; Mengin-Lecreulx, D.; Lemaitre, B. Drosophila Immunity: Analysis of PGRP-SB1 Expression, Enzymatic Activity and Function. PLOS ONE 2011, 6, e17231. [Google Scholar] [CrossRef]
- Bischoff, V.; Vignal, C.; Duvic, B.; Boneca, I.G.; Hoffmann, J.A.; Royet, J. Downregulation of the Drosophila Immune Response by Peptidoglycan-Recognition Proteins SC1 and SC2. PLOS Pathog. 2006, 2, e14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Basbous, N.; Coste, F.; Leone, P.; Vincentelli, R.; Royet, J.; Kellenberger, C.; Roussel, A. The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway. EMBO Rep. 2011, 12, 327–333. [Google Scholar] [CrossRef] [PubMed]
- Neyen, C.; Runchel, C.; Schüpfer, F.; Meier, P.; Lemaitre, B. The regulatory isoform rPGRP-LC induces immune resolution via endosomal degradation of receptors. Nat. Immunol. 2016, 17, 1150–1158. [Google Scholar] [CrossRef]
- Kleino, A.; Myllymäki, H.; Kallio, J.; Vanha-aho, L.-M.; Oksanen, K.; Ulvila, J.; Hultmark, D.; Valanne, S.; Rämet, M. Pirk Is a Negative Regulator of the Drosophila Imd Pathway. J. Immunol. 2008, 180, 5413. [Google Scholar] [CrossRef]
- Aggarwal, K.; Rus, F.; Vriesema-Magnuson, C.; Ertürk-Hasdemir, D.; Paquette, N.; Silverman, N. Rudra Interrupts Receptor Signaling Complexes to Negatively Regulate the IMD Pathway. PLOS Pathog. 2008, 4, e1000120. [Google Scholar] [CrossRef] [PubMed]
- Thevenon, D.; Engel, E.; Avet-Rochex, A.; Gottar, M.; Bergeret, E.; Tricoire, H.; Benaud, C.; Baudier, J.; Taillebourg, E.; Fauvarque, M.-O. The Drosophila Ubiquitin-Specific Protease dUSP36/Scny Targets IMD to Prevent Constitutive Immune Signaling. Cell Host Microbe 2009, 6, 309–320. [Google Scholar] [CrossRef] [PubMed]
- Yagi, Y.; Lim, Y.-M.; Tsuda, L.; Nishida, Y. Fat facets induces polyubiquitination of Imd and inhibits the innate immune response in Drosophila. Genes Cells 2013, 18, 934–945. [Google Scholar] [CrossRef]
- Tsichritzis, T.; Gaentzsch, P.C.; Kosmidis, S.; Brown, A.E.; Skoulakis, E.M.; Ligoxygakis, P.; Mosialos, G. A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense. Development 2007, 134, 2605–2614. [Google Scholar] [CrossRef]
- Trompouki, E.; Hatzivassiliou, E.; Tsichritzis, T.; Farmer, H.; Ashworth, A.; Mosialos, G. CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members. Nature 2003, 424, 793–796. [Google Scholar] [CrossRef]
- Kovalenko, A.; Chable-Bessia, C.; Cantarella, G.; Israël, A.; Wallach, D.; Courtois, G. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature 2003, 424, 801–805. [Google Scholar] [CrossRef]
- Tusco, R.; Jacomin, A.-C.; Jain, A.; Penman, B.S.; Larsen, K.B.; Johansen, T.; Nezis, I.P. Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses. Nat. Commun. 2017, 8, 1264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tsuda, M.; Langmann, C.; Harden, N.; Aigaki, T. The RING-finger scaffold protein Plenty of SH3s targets TAK1 to control immunity signalling in Drosophila. EMBO Rep. 2005, 6, 1082–1087. [Google Scholar] [CrossRef] [PubMed]
- Fernando, M.D.A.; Kounatidis, I.; Ligoxygakis, P. Loss of Trabid, a new negative regulator of the drosophila immune-deficiency pathway at the level of TAK1, reduces life span. PLoS Genet. 2014, 10, e1004117. [Google Scholar] [CrossRef] [PubMed]
- Bond, D.; Foley, E. A Quantitative RNAi Screen for JNK Modifiers Identifies Pvr as a Novel Regulator of Drosophila Immune Signaling. PLOS Pathog. 2009, 5, e1000655. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.; Lee, J.H.; Lee, S.Y.; Kim, E.; Chung, J. Caspar, a suppressor of antibacterial immunity in Drosophila. Proc. Natl. Acad. Sci. USA 2006, 103, 16358–16363. [Google Scholar] [CrossRef]
- Song, E.J.; Yim, S.-H.; Kim, E.; Kim, N.-S.; Lee, K.-J. Human Fas-Associated Factor 1, Interacting with Ubiquitinated Proteins and Valosin-Containing Protein, Is Involved in the Ubiquitin-Proteasome Pathway. Mol. Cell. Biol. 2005, 25, 2511–2524. [Google Scholar] [CrossRef]
- Foley, E.; O’Farrell, P.H. Functional Dissection of an Innate Immune Response by a Genome-Wide RNAi Screen. PLOS Biol. 2004, 2, e203. [Google Scholar] [CrossRef]
- Guntermann, S.; Primrose, D.A.; Foley, E. Dnr1-dependent regulation of the Drosophila immune deficiency signaling pathway. Dev. Comp. Immunol. 2009, 33, 127–134. [Google Scholar] [CrossRef]
- Salem Wehbe, L.; Barakat, D.; Acker, A.; El Khoury, R.; Reichhart, J.-M.; Matt, N.; El Chamy, L. Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Drosophila Immune Response. J. Immunol. 2021, 207, 1616. [Google Scholar] [CrossRef]
- Ryu, J.-H.; Kim, S.-H.; Lee, H.-Y.; Bai, J.Y.; Nam, Y.-D.; Bae, J.-W.; Lee, D.G.; Shin, S.C.; Ha, E.-M.; Lee, W.-J. Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila. Science 2008, 319, 777–782. [Google Scholar] [CrossRef]
- Ji-Hwan, R.; Ki-Bum, N.; Chun-Taek, O.; Hyuck-Jin, N.; Sung-Hee, K.; Joo-Heon, Y.; Je-Kyeong, S.; Mi-Ae, Y.; In-Hwan, J.; Paul, T.B.; et al. The Homeobox Gene Caudal Regulates Constitutive Local Expression of Antimicrobial Peptide Genes in Drosophila Epithelia. Mol. Cell. Biol. 2004, 24, 172–185. [Google Scholar]
- Myllymäki, H.; Rämet, M. Transcription factor zfh1 downregulates Drosophila Imd pathway. Dev. Comp. Immunol. 2013, 39, 188–197. [Google Scholar] [CrossRef] [PubMed]
- Kim, L.K.; Choi, U.Y.; Cho, H.S.; Lee, J.S.; Lee, W.; Kim, J.; Jeong, K.; Shim, J.; Kim-Ha, J.; Kim, Y.-J. Down-Regulation of NF-κB Target Genes by the AP-1 and STAT Complex during the Innate Immune Response in Drosophila. PLOS Biol. 2007, 5, e238. [Google Scholar] [CrossRef]
- Dantoft, W.; Davis, M.M.; Lindvall, J.M.; Tang, X.; Uvell, H.; Junell, A.; Beskow, A.; Engström, Y. The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota. BMC Biol. 2013, 11, 99. [Google Scholar] [CrossRef] [PubMed]
- Ji, Y.; Thomas, C.; Tulin, N.; Lodhi, N.; Boamah, E.; Kolenko, V.; Tulin, A.V. Charon Mediates Immune Deficiency–Driven PARP-1–Dependent Immune Responses in Drosophila. J. Immunol. 2016, 197, 2382. [Google Scholar] [CrossRef]
- Shibata, T.; Sekihara, S.; Fujikawa, T.; Miyaji, R.; Maki, K.; Ishihara, T.; Koshiba, T.; Kawabata, S.-I. Transglutaminase-catalyzed protein-protein cross-linking suppresses the activity of the NF-κB-like transcription factor relish. Sci. Signal 2013, 6, ra61. [Google Scholar] [CrossRef]
- Maki, K.; Shibata, T.; Kawabata, S. Transglutaminase-catalyzed incorporation of polyamines masks the DNA-binding region of the transcription factor Relish. J. Biol. Chem. 2017, 292, 6369–6380. [Google Scholar] [CrossRef]
- Aparicio, R.; Neyen, C.; Lemaitre, B.; Busturia, A. dRYBP contributes to the negative regulation of the Drosophila Imd pathway. PLoS ONE 2013, 8, e62052. [Google Scholar] [CrossRef]
- Celen, A.B.; Sahin, U. Sumoylation on its 25th anniversary: Mechanisms, pathology, and emerging concepts. FEBS J. 2020, 287, 3110–3140. [Google Scholar] [CrossRef]
- Tang, R.; Huang, W.; Guan, J.; Liu, Q.; Beerntsen, B.T.; Ling, E. Drosophila H2Av negatively regulates the activity of the IMD pathway via facilitating Relish SUMOylation. PLOS Genet. 2021, 17, e1009718. [Google Scholar] [CrossRef]
- Prakash, P.; Roychowdhury-Sinha, A.; Goto, A. Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila. Sci. Rep. 2021, 11, 15549. [Google Scholar] [CrossRef]
- Goto, A.; Matsushita, K.; Gesellchen, V.; Chamy, L.E.; Kuttenkeuler, D.; Takeuchi, O.; Hoffmann, J.A.; Akira, S.; Boutros, M.; Reichhart, J.M. Akirins are highly conserved nuclear proteins required for NF-κB-dependent gene expression in drosophila and mice. Nat. Immunol. 2007, 9, 97. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tartey, S.; Matsushita, K.; Vandenbon, A.; Ori, D.; Imamura, T.; Mino, T.; Standley, D.M.; Hoffmann, J.A.; Reichhart, J.-M.; Akira, S.; et al. Akirin2 is critical for inducing inflammatory genes by bridging IκB-ζ and the SWI/SNF complex. EMBO J. 2014, 33, 2332. [Google Scholar] [CrossRef] [PubMed]
- Nowak, S.J.; Baylies, M.K. Akirin: A context-dependent link between transcription and chromatin remodeling. Bioarchitecture 2012, 2, 209–213. [Google Scholar] [CrossRef] [PubMed]
- Cammarata-Mouchtouris, A.; Nguyen, X.-H.; Acker, A.; Bonnay, F.; Goto, A.; Orian, A.; Fauvarque, M.-O.; Boutros, M.; Reichhart, J.-M.; Matt, N. Hyd ubiquitinates the NF-κB co-factor Akirin to operate an effective immune response in Drosophila. PLOS Pathog. 2020, 16, e1008458. [Google Scholar] [CrossRef]
- Bonnay, F.; Nguyen, X.-H.; Cohen-Berros, E.; Troxler, L.; Batsche, E.; Camonis, J.; Takeuchi, O.; Reichhart, J.-M.; Matt, N. Akirin specifies NF-κB selectivity of Drosophila innate immune response via chromatin remodeling. EMBO J. 2014, 33, 2349–2362. [Google Scholar] [CrossRef]
- Hildebrand, D.G.; Alexander, E.; Hörber, S.; Lehle, S.; Obermayer, K.; Münck, N.-A.; Rothfuss, O.; Frick, J.-S.; Morimatsu, M.; Schmitz, I.; et al. IκBζ Is a Transcriptional Key Regulator of CCL2/MCP-1. J. Immunol. 2013, 190, 4812. [Google Scholar] [CrossRef]
- Kannan, Y.; Yu, J.; Raices, R.M.; Seshadri, S.; Wei, M.; Caligiuri, M.A.; Wewers, M.D. IκBζ augments IL-12– and IL-18–mediated IFN-γ production in human NK cells. Blood 2011, 117, 2855–2863. [Google Scholar] [CrossRef]
- Kohda, A.; Yamazaki, S.; Sumimoto, H. DNA element downstream of the κB site in the Lcn2 promoter is required for transcriptional activation by IκBζ and NF-κB p50. Genes Cells 2014, 19, 620–628. [Google Scholar] [CrossRef]
- Yamamoto, M.; Yamazaki, S.; Uematsu, S.; Sato, S.; Hemmi, H.; Hoshino, K.; Kaisho, T.; Kuwata, H.; Takeuchi, O.; Takeshige, K.; et al. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. Nature 2004, 430, 218. [Google Scholar] [CrossRef]
- Naranjo, V.; Ayllón, N.; Pérez de la Lastra, J.M.; Galindo, R.C.; Kocan, K.M.; Blouin, E.F.; Mitra, R.; Alberdi, P.; Villar, M.; de la Fuente, J. Reciprocal Regulation of NF-kB (Relish) and Subolesin in the Tick Vector, Ixodes scapularis. PLoS ONE 2013, 8, e65915. [Google Scholar] [CrossRef] [PubMed]
- Polanowska, J.; Chen, J.-X.; Soulé, J.; Omi, S.; Belougne, J.; Taffoni, C.; Pujol, N.; Selbach, M.; Zugasti, O.; Ewbank, J.J. Evolutionary plasticity in the innate immune function of Akirin. PLoS Genet. 2018, 14, e1007494. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bosch, P.J.; Peek, S.L.; Smolikove, S.; Weiner, J.A. Akirin proteins in development and disease: Critical roles and mechanisms of action. Cell. Mol. Life Sci. 2020, 77, 4237–4254. [Google Scholar] [CrossRef] [PubMed]
- Valanne, S.; Järvelä-Stölting, M.; Harjula, S.-K.E.; Myllymäki, H.; Salminen, T.S.; Rämet, M. Osa-Containing Brahma Complex Regulates Innate Immunity and the Expression of Metabolic Genes in Drosophila. J. Immunol. 2020, 204, 2143. [Google Scholar] [CrossRef] [PubMed]
- Nowak, S.J.; Aihara, H.; Gonzalez, K.; Nibu, Y.; Baylies, M.K. Akirin Links Twist-Regulated Transcription with the Brahma Chromatin Remodeling Complex during Embryogenesis. PLoS Genet. 2012, 8, e1002547. [Google Scholar] [CrossRef] [PubMed]
- Fukuyama, H.; Verdier, Y.; Guan, Y.; Makino-Okamura, C.; Shilova, V.; Liu, X.; Maksoud, E.; Matsubayashi, J.; Haddad, I.; Spirohn, K.; et al. Landscape of protein–protein interactions in Drosophila immune deficiency signaling during bacterial challenge. Proc. Natl. Acad. Sci. USA 2013, 110, 10717. [Google Scholar] [CrossRef]
- Goto, A.; Fukuyama, H.; Imler, J.-L.; Hoffmann, J.A. The Chromatin Regulator DMAP1 Modulates Activity of the Nuclear Factor κB Transcription Factor Relish in the Drosophila Innate Immune Response. J. Biol. Chemist. 2014, 289, 20470–20476. [Google Scholar] [CrossRef]
- He, X.; Yu, J.; Wang, M.; Cheng, Y.; Han, Y.; Yang, S.; Shi, G.; Sun, L.; Fang, Y.; Gong, S.; et al. Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice. Nat. Microbiol. 2017, 2, 17056. [Google Scholar] [CrossRef]
- de Almeida, M.; Hinterndorfer, M.; Brunner, H.; Grishkovskaya, I.; Singh, K.; Schleiffer, A.; Jude, J.; Deswal, S.; Kalis, R.; Vunjak, M.; et al. AKIRIN2 controls the nuclear import of proteasomes in vertebrates. Nature 2021, 599, 491–496. [Google Scholar] [CrossRef]
- Luecke, S.; Sheu, K.M.; Hoffmann, A. Stimulus-specific responses in innate immunity: Multilayered regulatory circuits. Immunity 2021, 54, 1915–1932. [Google Scholar] [CrossRef]
Pathway Members | Sensors/Adaptors | Inhibitors |
---|---|---|
At the membrane level | PGRP-LC | PGRP-LB PGRP-SB PGRP-SC PGRP-LF Pirk |
In the cytosol | PGRP-LE IMD FADD Dredd dIAP2 Eff Ben Uev1A TAB2 TAK1 IKKβ IKKγ Leswright Relish (Full) | Verloren dUSP36 Faf Trabid POSH PP4 CYLD Caspar Dnr1 |
In the nucleus | Relish (N-terminal) Hyd Akirin Bap60 Osa | dAP-1 Stat92E DSP1 HDAC1 Caudal Zfh1 H2Av |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cammarata-Mouchtouris, A.; Acker, A.; Goto, A.; Chen, D.; Matt, N.; Leclerc, V. Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila. Biomedicines 2022, 10, 2304. https://doi.org/10.3390/biomedicines10092304
Cammarata-Mouchtouris A, Acker A, Goto A, Chen D, Matt N, Leclerc V. Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila. Biomedicines. 2022; 10(9):2304. https://doi.org/10.3390/biomedicines10092304
Chicago/Turabian StyleCammarata-Mouchtouris, Alexandre, Adrian Acker, Akira Goto, Di Chen, Nicolas Matt, and Vincent Leclerc. 2022. "Dynamic Regulation of NF-κB Response in Innate Immunity: The Case of the IMD Pathway in Drosophila" Biomedicines 10, no. 9: 2304. https://doi.org/10.3390/biomedicines10092304