Hierarchical layers of gene control in the innate response to infection
NETWORK CONTRIBUTION
Infection causes drastic shifts in gene expression towards antimicrobial gene signatures. We will examine the transcriptional response of bone marrow macrophages to infection with the intracellular bacterium Listeria monocytogenes (Lm), focusing on changes to diagnostic chromatin modifications, DNA accessibility and intra- as well as interchromosomal interactions. We will concentrate on STAT-dependent type I interferon (IFN-I)-induced genes (ISG) and a group of ‘synergy genes’, whose promoter activation requires cooperative activity of the IFN-I/STAT and NFkappaB pathways. ISG and synergy genes represent distinct regulatory entities and we shall examine their chromatin landscapes for differences before and following infection.
Our major goal is to derive a comprehensive view of how STATs determine genome structure and chromatin landscapes and thereby coordinating gene transcription during microbial infection.
Within the project we aim to determine how diverse regulatory input to ISG and synergy genes derives from different chromosomal topologically associated domains (TAD). Genome editing will be used to validate the functional relevance of enhancers that regulate ISG and synergy genes.
PUBLICATIONS
SFB-F61 / F28 related publications - Group Decker/Farlik
| Ramsauer, K., Farlik, M., Zupkovitz, G., Seiser, C., Kröger, A., Hauser, H.J. and Decker, T. (2007). Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-γ-inducible gbp2 gene. Proc Natl Acad Sci USA 104:2849-54. doi: 10.1073/pnas.0610944104 |
| Schroder, K., Spille, M., Pilz, A., Lattin, J., Bode, K.A., Irvine, K.M., Burrows, A.D., Ravasi, T., Weighardt, H., Stacey, K.J., Decker, T., Hume, D.A., Dalpke, A.H. and Sweet, M.J. (2007). Differential effects of CpG DNA on IFNβ induction and STAT1 activation in murine macrophages versus dendritic cells: alternatively activated STAT1 negatively regulates toll-like receptor signalling in macrophages. J Immunol 179(6):3495-503. doi: 10.4049/jimmunol.179.6.3495 |
| Werts, C., Le Bourhis, L., Liu, J., Magalhaes, J.G., Fritz, J.H., Stockinger, S., Decker, T., Philpott, D., Ma, X. and Girardin, S.E. (2007). Nod1 and Nod2 induce CCL5/RANTES through the NFκB pathway. Eur J Immunol 37(9):2499-508. doi: 10.1002/eji.200737069 |
| Reutterer, B., Stockinger, S., Pilz, A., Soulat, S., Kastner, R., Westermayer, S., Rülicke, T., Müller, M. and Decker, T. (2008). Type I IFN are host modulators of strain-specific Listeria monocytogenes virulence. Cell Microbiol 10:1116-29. doi: 10.1111/j.1462-5822.2007.01114.x |
| Huber, M., Steinwald, V., Guralnik, A., Brüstle, A., Kleemann, P., Rosenplänter, C., Decker, T. and Lohoff, M. (2008). IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 20:223-34. doi: 10.1093/intimm/dxm139 |
| Soulat, D., Bürckstümmer, T., Westermayer, S., Goncalves, A., Bauch, A., Preradovic, A., Hantschel, O., Bennett, K.L., Decker*, T. and Superti-Furga*, G. (2008). *corresponding authors The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J 27:2135-46. doi: 10.1038/emboj.2008.126 |
| Zwaferink, H., Stockinger, S., Hazemi, P., Lemmens-Gruber, R. and Decker, T. (2008). IFNβ increases Listeriolysin O-induced membrane permeabilisation and death of macrophages. J Immunol 180:4116-23. doi: 10.4049/jimmunol.180.6.4116 |
| Zwaferink, H., Stockinger, S., Reipert, S. and Decker, T. (2008). Stimulation of inducible nitric oxide synthase expression by interferon beta increases necrotic death of macrophages upon Listeria monocytogenes infection. Infect Immun 76:1649-56. doi: 10.1128/IAI.01251-07 |
| von Gabain, A., Nagy, E. and Decker, T. (2008). Novel paradigms in vaccine development: from small pox eradication to therapeutic vaccines. Biol Chem 389:455-6. [commentary] doi: 10.1515/BC.2008.067 |
| Stockinger, S. and Decker, T. (2008). New functions of type I interferons revealed by infection studies with Listeria monocytogenes. Immunobiol 213:889-97. [review] doi: 10.1016/j.imbio.2008.07.020 |
| Pilz, A., Kratky, W., Stockinger, S., Simma, O., Kalinke, U., Lingnau, K., von Gabain, A., Stoiber, D., Sexl, V., Kolbe, T., Rulicke, T., Müller, M. and Decker, T. (2009). Dendritic cells require STAT-1 phosphorylated at its transactivating domain for the induction of peptide-specific CTL. J Immunol 183:2286-93. doi: 10.4049/jimmunol.0901383 |
| Prchal, M, Pilz, A., Simma, O., Lingnau, K., von Gabain, A., Strobl, B., Müller, M., and Decker, T. (2009). Type I interferons as mediators of immune adjuvants for T- and B cell- dependent acquired immunity. Vaccine 27 Suppl 6, G17-20. doi: 10.1016/j.vaccine.2009.10.016 |
| Simma, O., Zebedin, E., Neugebauer, N., Schellack, C., Pilz, A., Chang-Rodriguez, S., Lingnau, K., Weisz, E., Putz, E.M., Pickl, W.F., Felzmann, T., Müller, M., Decker, T., Sexl, V. and Stoiber, D. (2009). Identification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillance. Cancer Res 69:203-11. doi: 10.1158/0008-5472.CAN-08-1705 |
| Stockinger, S., Kastner, R., Kernbauer, E., Pilz, A., Westermayer, S., Reutterer, B., Soulat, D., Stengl, G., Vogl, C., Frenz, T., Waibler, Z., Taniguchi, T., Rulicke, T., Kalinke, U., Müller, M. and Decker, T. (2009). Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. PLoS Pathog 5, e1000355. doi: 10.1371/journal.ppat.1000355 |
| Aly, S., Mages, J., Reiling, N., Kalinke, U., Decker, T., Lang, R. and Ehlers, S. (2009). Mycobacteria-induced granuloma necrosis depends on IRF-1. J Cell Mol Med 13:2069-2082. doi: 10.1111/j.1582-4934.2008.00470.x |
| Grundtner, P., Gruber, S., Murray, S.S., Vermeire, S., Rutgeerts, P., Decker, T., Lakatos, P.L. and Gasche, C. (2009). The IL10R1 S138G loss-of-function allele and ulcerative colitis. Genes Immun 10:84-92. doi: 10.1038/gene.2008.72 |
| Maldonado, R.A., Soriano, M.A., Perdomo, C., Sigrist, K., Irvine, D.J., Decker, T. and Glimcher, L.H. (2009). Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med 206(4):877-92. doi: 10.1084/jem.20082900 |
| Plumlee, C.R., Lee, C., Song, L., Prince, A., Beg, A., Decker, T., Shuman, H.A. and. Schindler, C. (2009). Interferons direct an effective innate response to Legionella pneumophila infection. J Biol Chem 284:30058-30066. doi: 10.1074/jbc.M109.018283 |
| Stockinger, S. and Decker, T. (2009). STATs and infection. In JAK-STAT Pathways in Disease (Stephanou, A., Ed.). Landes Biosci, Austin, TX. pp. 43-57. [book chapter] ISBN-13: 978-1587063152 |
| Farlik, M., Reutterer, B., Schindler, C., Greten, F., Vogl, C., Müller, M., and Decker, T. (2010). Nonconventional Initiation Complex Assembly by STAT and NF-kappaB Transcription Factors Regulates Nitric Oxide Synthase Expression. Immunity 33: 25-34. doi: 10.1016/j.immuni.2010.07.001 |
| Bourgeois, C., Majer, O., Frohner, I.E., Lesiak-Markowicz, I., Hildering, K.S., Glaser, W., Stockinger, S., Decker, T., Akira, S., Müller, M., and Kuchler, K. (2011). Conventional dendritic cells mount a type I interferone response against Candida spp requiring novel phagosomal TLR7 mediated IFN-β signaling. J Immunol 186, 3104-3112. doi: 10.4049/jimmunol.1002599 |
| Schneckenleithner, C., Bago-Horvath, Z., Dolznig, H., Neugebauer, N., Kollmann, K., Kolbe, T., Decker, T., Kerjaschki, D., Wagner, K.-U., Müller, M., Stoiber, D., and Sexl, V. (2011). Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias. Oncotarget 2: 1043-1054. online ISSN: 1949-2553 |
| Kernbauer, E., Maier, V., Stoiber, D., Strobl, B., Schneckenleithner, C., Sexl, V., Reichart, U., Kalinke, U., Reizis, B., Jamieson, A., Müller, M., and Decker, T. (2012). Conditional Stat1 ablation reveals the importance of interferon signaling for immunity to Listeria monocytogenes infection. PLoS Pathog 8: e1002763. doi: 10.1371/journal.ppat.1002763 |
| Wallner*, B., Leitner*, N.R., Vielnascher, R.M., Kernbauer, E., Kolbe, T., Karaghiosoff, M., Rülicke, T., Decker, T., and Müller, M. (2012). *equal contribution Generation of mice with a conditional Stat1 null allele. Transgenic Res 21: 217-224. doi: 10.1007/s11248-011-9519-5 |
| Decker, T., and Müller, M. (2012). Jak-Stat Signaling: From Basics to Disease. Jak-Stat Signaling: From Basics to Disease. Springer Wien Heidelberg New York Dordrecht London. 448 p. 45 illus. [book] doi: 10.1007/978-3-7091-0891-8_1 ISBN: 978-3-7091-0890-1 |
| Decker, T., and Müller, M. (2012) The Continuing Fascination with Jaks and Stats: An Introduction. Jak-Stat Signaling: From Basics to Disease. Springer Wien Heidelberg New York Dordrecht London. pp. 1-4. [book chapter] doi: 10.1007/978-3-7091-0891-8_1 |
| Rampetsreiter, P. and Eferl, R. (2012). STAT1 and STAT3 Transcription Factors in Inflammation-Associated Colon Cancer. In Jak-Stat Signaling: From Basics to Disease. (Decker, T. and Müller, M. Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 289-304. [book chapter] doi: 10.1007/978-3-7091-0891-8_16 ISBN: 978-3-7091-0890-1 |
| Aubry*, C., Corr*, S.C., Wienerroither*, S., Goulard, C., Jones, R., Jamieson, A.M., Decker, T., O'Neill, L.A., Dussurget, O., and Cossart, P. (2012). *equal contribution Both TLR2 and TRIF Contribute to Interferon-beta Production during Listeria Infection. PLoS One 7: e33299. doi: 10.1371/journal.pone.0033299 |
| Aubry*, C., Corrd*, S., Wienerroither*, S., Goulard, C., Jones, R., Jamieson, A., Decker, T., O'Neill, T., Dussurget, O. and P. Cossart (2012). *equal contribution A TLR2, TLR3 and TRIF-dependent interferon-β response to bacterial infection. PLoS One 7: e33299. doi: 10.1371/journal.pone.0033299 |
| Farlik, M., Rapp, B., Marie, I., Levy, D.E., Jamieson, A.M., and Decker, T. (2012). Contribution of a TBK1-IRF7 pathway to IFN-gamma-induced gene expression. Mol Cell Biol 32: 1032-1043 doi: 10.1128/MCB.06021-11 |
| Jamieson, A., Farlik, M., and Decker, T. (2012). How Stats Interact with the Molecular Machinery of Transcriptional Activation. In Jak-Stat Signaling: From Basics to Disease. (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 65-90. [book chapter] doi: 10.1007/978-3-7091-0891-8_5 ISBN: 978-3-7091-0890-1 |
| Nivarthi, H., Friedbichler, K., and Moriggl, R. (2012). Stat5 as a Hematopoietic Master Regulator for Differentiation and Neoplasia Development. In Jak-Stat Signaling: From Basics to Disease. (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 153-168. [book chapter] doi: 10.1007/978-3-7091-0891-8_10 ISBN: 978-3-7091-0890-1 |
| Strobl, B., Leitner, N.R., and Müller, M. (2012). Multifaceted Antiviral Actions of Interferon-Stimulated Gene Products. In Jak-Stat Signaling: From Basics to Disease. (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 387-424. [book chapter] doi: 10.1007/978-3-7091-0891-8_21 ISBN: 978-3-7091-0890-1 |
| Putz, E.M., Zebedin, E., and Sexl, V. (2012). STAT Transcription Factors: Controlling All Aspects of NK Cell Biology. In Jak-Stat Signaling: From Basics to Disease (Decker, T. and Müller, M., Eds.) Springer Wien Heidelberg New York Dordrecht London. pp. 187-204. [book chapter] doi: 10.1007/978-3-7091-0891-8_12 ISBN: 978-3-7091-0890-1 |
| Rauch, I., Müller, M., and Decker, T. (2013). The regulation of inflammation by interferons and their STATs. JAK-STAT 2:1, e23820. [review] doi: 10.4161/jkst.23820 |
| Kernbauer*, E., Maier*, V., Rauch, I., Müller, M. and Decker, T. (2013). *equal contribution Route of infection determines the impact of type I interferons on innate immunity to Listeria monocytogenes. PLoS One 8: e65007. doi: 10.1371/journal.pone.0065007 |
| Köprülü, A.D., Kastner, R., Wienerroither, S., Lassnig, C., Putz, E.-M., Majer, O., Reutterer, B., Sexl, V., Kuchler, K., Müller, M., Decker, T., and Ellmeier, W. (2013). The tyrosine kinase Btk regulates the macrophage response to Listeria monocytogenes infection. PLoS One 8: e60476. doi: 10.1371/journal.pone.0060476 |
| Putz, E.M., Gotthardt, D., Hoermann, G., Csiszar, A., Wirth, S., Berger, A., Straka, E., Rigler, D., Wallner, B., Jamieson, A.M., Pickl, W.F., Zebedin-Brandl, E.M., Müller, M., Decker, T., and Sexl, V. (2013). CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance. Cell Rep 15: 437-444. doi: 10.1016/j.celrep.2013.07.012 |
| Semper, C., Leitner, N.R., Lassnig, C., Parrini, M., Mahlakoiv, T., Rammerstorfer, M., Lorenz, K., Rigler, D., Müller, S., Kolbe, T., Vogl, C., Rülicke, T., Staeheli, P., Decker, T., Müller, M., and Strobl, B. (2014). STAT1β is not dominant negative and is capable of contributing to IFNγ-dependent innate immunity. Mol Cell Biol 34: 2235-2248. doi: 10.1128/MCB.00295-14 |
| Wienerroither, S., Rauch, I., Rosebrock, F., Jamieson, A.M., Bradner, J., Muhar, M., Zuber, J., Müller, M., and Decker, T. (2014). Regulation of NO synthesis, local inflammation and innate immunity to pathogens by BET family proteins. Mol Cell Biol 34: 415-427. doi: 10.1128/MCB.01353-13 |
| Begitt, A., Droescher, M., Meyer, T., Schmid, C.D., Baker, M., Antunes, F., Owen, M.R., Naumann, R., Decker, T., and Vinkemeier, U. (2014). STAT1-cooperative DNA binding distinguishes type-1 from type-2 interferon signaling. Nat Immunol 15: 168-176. doi: 10.1038/ni.2794 |
| Rauch, I., Rosebrock, F., Hainzl, E., Heider, S., Majoros, A., Wienerroither, S., Strobl, B., Stockinger, S., Müller, M., Kenner, L., and Decker, T. (2015). Noncanonical effects of IRF9 in intestinal inflammation: more than type I and type III interferons. Mol Cell Biol 35: 2332-2343 doi: 10.1128/MCB.01498-14 |
| Wienerroither, S., Shukla, P., Farlik, M., Majoros, A., Stych, B., Vogl, C., Cheon, H., Stark, G.R., Strobl, B., Müller, M., and Decker, T. (2015). Cooperative transcriptional activation of antimicrobial genes by STAT and NFκB pathways through concerted recruitment of the mediator complex. Cell Reports 12: 1-13. doi: http://dx.doi.org/10.1016/j.celrep.2015.06.021 |
| Abdul-Sater, A.A., Majoros, A., Plumlee, C.R., Perry, S., Gu, A.D., Lee, C., Shresta, S., Decker, T., and Schindler, C. (2015). Different STAT Transcription Complexes Drive Early and Delayed Responses to Type I IFNs. J Immunol May 27. pii: 1401139. [Epub ahead of print] doi: 10.4049/jimmunol.1401139 |
| Berry, D., Kuzyk, O., Rauch, I., Heider, S., Schwab, C., Hainzl, E., Decker, T., Müller, M., Strobl, B., Schleper, C., Urich, T., Wagner, M., Kenner, L., and Loy, A. (2015). Intestinal microbiota signatures associated with inflammation history in mice experiencing recurring colitis Front Microbiol. 2015; 6: 1408. doi: 10.3389/fmicb.2015.01408 |
| Hainzl, E., Stockinger, S., Rauch, I., Heider, S., Berry, D., Lassnig, C., Schwab, C., Rosebrock, F., Milinovich, G., Schlederer, M., Wagner, M., Schleper, C., Loy, A., Urich, T., Kenner, L., Han, X., Decker, T., Strobl, B., and Muller, M. (2015). Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis. Journal of immunology 195, 5011-5024. Journal of immunology 195, 5011-5024 |
| Decker, T. (2016). Emancipation from transcriptional latency: unphosphorylated STAT5 as guardian of hematopoietic differentiation. The EMBO journal 35, 555-557 |
| Majoros, A., Platanitis, E., Szappanos, D., Cheoan, H.J., Vogl, C., Shukla, P., Stark, G.R., Sexl, V., Schreiber, R.D., Schindler, C., Müller, M., and Decker, T. (2016). Response to interferons and antibacterial innate immunity in absence of tyrosine-phosphorylated STAT1. EMBO Rep 17, 367-382 |
| Putz, E.M., Majoros, A., Gotthart, D., Prchal-Murphy, M., Zebedin-Brandl, E., Fux, D.A., Schlattl, A., Schreiber, R.D., Carotta, S., Müller, M., Gerner, C., Decker, T., and Sexl, V. (2016). Novel non-canonical role of STAT1 in Natural Killer cell cytotoxicity. OncoImmunology 10.1080/2162402X.2016.1186314. |
| Majoros, A., Platanitis, E., Kernbauer-Holzl, E., Rosebrock, F., Muller, M., and Decker, T. (2017). Canonical and Non-Canonical Aspects of JAK-STAT Signaling: Lessons from Interferons for Cytokine Responses. Front Immunol 8, 29 |
| Parrini, M., Meissl, K., Ola, M.J., Lederer, T., Puga, A., Wienerroither, S., Kovarik, P., Decker, T., Müller, M. and Strobl, B. The C-terminal transactivation domain of STAT1 has a gene-specific role in transactivation and cofactor recruitment Front Immunol. 2018 Dec 6;9(2879). doi: 10.3389/fimmu.2018.02879 |
| Platanitis, E. and Decker, T. Regulatory networks involving STATs, IRFs, and NFkB in inflammation Front Immunol. 2018 Nov 13;9:2542. doi: 10.3389/fimmu.2018.02542. eCollection 2018 |
| Porpaczy, E., Tripolt, S., Hoelbl-Kovacic, A., Gisslinger, B., Bago-Horvath, Z., Casanova-Hevia, E., Clappier, E., Decker, T., Fajmann, S., Fux, D. A., Greiner, G., Gueltekin, S., Heller, G., Herkner, H., Hoermann, G., Kiladjian, J. J., Kolbe, T., Kornauth, C., Krauth, M. T., Kralovics, R., Muellauer, L., Mueller, M., Prchal-Murphy, M., Putz, E. M., Raffoux, E., Schiefer, A. I., Schmetterer, K., Schneckenleithner, C., Simonitsch-Klupp, I., Skrabs, C., Sperr, W. R., Staber, P. B., Strobl, B., Valent, P., Jaeger, U., Gisslinger, H. and Sexl, V. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy Blood. 2018 Jun 14. pii: blood-2017-10-810739. doi: 10.1182/blood-2017-10-810739 |
| Kollmann, S., Grundschober, E., Maurer, B., Warsch, W., Grausenburger, R., Edlinger, L., Huuhtanen, J., Lagger, S., Hennighausen, L., Valent, P., Decker, T., Strobl, B., Mueller, M., Mustjoki, S., Hoelbl-Kovacic, A. and Sexl, V. Twins with different personalities: STAT5B-but not STAT5A-has a key role in BCR/ABL-induced leukemia Leukemia. 2019 Jan 24. pii: 10.1038/s41375-018-0369-5. doi: 10.1038/s41375-018-0369-5 |
| Platanitis, E., Demiroz, D., Schneller, A., Fischer, K., Capelle, C., Hartl, M., Gossenreiter, T., Muller, M., Novatchkova, M. and Decker, T. A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription Nat Commun. 2019 Jul 2;10(1):2921. doi: 10.1038/s41467-019-10970-y |
| Fischer, K., Tschismarov, R., Pilz, A., Straubinger, S., Carotta, S., McDowell, A., and Decker, T. Cutibacterium acnes Infection Induces Type I Interferon Synthesis Through the cGAS-STING Pathway Front Immunol 11, 571334. doi: 10.3389/fimmu.2020.571334 |
| Romanov, R.A., Tretiakov, E.O., Kastriti, M.E., Zupancic, M., Häring, M., Korchynska, S., Popadin, K., Benevento, M., Rebernik, P., Lallemend, F., Nishimori, K., Clotman, F., Andrews, W.D., Parnavelas, J.G., Farlik, M., Bock, C., Adameyko, I., Hökfelt, T., Keimpema, E., and Harkany, T. Molecular design of hypothalamus development Nature 582, 246-252. Doi: 10.1038/s41586-020-2266-0 |
| Demiroz, D., Platanitis, E., Bryant, M., Fischer, P., Prchal-Murphy, M., Lercher, A., Lassnig, C., Baccarini, M., Müller, M., Bergthaler, A., Sexl, V., Dolezal, M., and Decker, T. Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons PLoS Pathog 2021 Jul 8;17, e1009697. doi: 10.1371/journal.ppat.1009697 |
| Novoszel, P., Drobits, B., Holcmann, M., Fernandes, C.S., Tschismarov, R., Derdak, S., Decker, T., Wagner, E.F., and Sibilia, M. The AP-1 transcription factors c-Jun and JunB are essential for CD8α conventional dendritic cell identity Cell Death Differ 28, 2404-2420. doi: 10.1038/s41418-021-00765-4 |
| Decker, T. The early interferon catches the SARS-CoV-2 J Exp Med 218, e20211667. doi: 10.1084/jem.20211667 |
