Deutsch
Latz lab
Understanding the links between innate immunity, chronic inflammatory disease and healthy ageing
Immunobiology of inflammation
The Eicke Latz laboratory is dedicated to uncovering the fundamental mechanisms of innate immune activation that play a crucial role in autoinflammatory, rheumatologic and chronic inflammatory diseases. Utilizing a blend of systems immunology, experimental biology, and human translational science, the lab seeks to understand how the innate immune system either maintains balance or contributes to the development of inflammatory diseases. The insights gained are crucial for a variety of auto-inflammatory, autoimmune, and chronic inflammatory conditions. To validate the significance of their discoveries, the laboratory utilizes preclinical models and reverse translational methods, which encompass the use of biomaterials sourced from patients and the implementation of observational clinical trials. The lab’s research has led to the identification of new therapeutic targets, resulting in the creation of several biotech companies aimed at converting these basic research discoveries into innovative treatments and preventive strategies.
Scientists
Cassandra Harapas, PhD
Pia Langhoff, PhD
Daniel Simpson, PhD
PhD students
Melanie Nuesch
Technical staff
Olga Pogasiy
Próchnicki T, Vasconcelos MB, Robinson KS, Mangan MSJ, De Graaf D, Shkarina K, Lovotti M, Standke L, Kaiser R, Stahl R, Duthie FG, Rothe M, Antonova K, Jenster LM, Lau ZH, Rösing S, Mirza N, Gottschild C, Wachten D, Günther C, Kufer TA, Schmidt FI, Zhong FL, Latz E. Mitochondrial damage activates the NLRP10 inflammasome. Nat Immunol. 2023 Apr;24(4):595-603.
Hochheiser IV, Pilsl M, Hagelueken G, Moecking J, Marleaux M, Brinkschulte R, Latz E, Engel C, Geyer M. Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3. Nature. 2022 Apr;604(7904):184-189.
Mario A Lauterbach, Jasmin E Hanke, Magdalini Serefidou, Matthew SJ Mangan, Carl-Christian Kolbe, Timo Hess, Maximilian Rothe, Romina Kaiser, Florian Hoss, Jan Gehlen, Gudrun Engels, Maike Kreutzenbeck, Susanne V Schmidt, Anette Christ, Axel Imhof, Karsten Hiller, Eicke Latz. Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via ATP-citrate lyase. Immunity. 2019 Dec 17; 51:6:997-1911
Hoss F, Mueller JL, Rojas Ringeling F, Rodriguez-Alcazar JF, Brinkschulte R, Seifert G, Stahl R, Broderick L, Putnam CD, Kolodner RD, Canzar S, Geyer M, Hoffman HM, Latz E. Alternative splicing regulates stochastic NLRP3 activity. Nat Commun. 2019 Jul 19;10(1):3238.
Karin Pelka, Damien Bertheloot, Elisa Reimer, Kshiti Phulphagar, Susanne V. Schmidt, Anette Christ, Rainer Stahl, Nicki Watson, Kensuke Miyake, Nir Hacohen, Albert Haas, Melanie M. Brinkmann, Ann Marshak-Rothstein, Felix Meissner and Eicke Latz. The chaperone UNC93B1 regulates toll-like receptor stability independent of endosomal TLR transport. Immunity. 2018 May 15;48(5):911-922.e7
Christ A, Günther P, Lauterbach MAR, Duewell P, Biswas D, Pelka K, Scholz CJ, Oosting M, Haendler K, Baßler K, Klee K, Schulte-Schrepping J, Ulas T, Moorlag SJCFM, Kumar V, Park MH, Joosten LAB, Groh LA, Riksen NP, Espevik T, Schlitzer A, Li Y, Fitzgerald ML, Netea MG, Schultze JL, Latz E. Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell. 2018 Jan 11;172(1-2):162-175.e14
Venegas C, Kumar S, Franklin BS, Dierkes T, Brinkschulte R, Tejera D, Vieira-Saecker A, Schwartz S, Santarelli F, Kummer MP, Griep A, Gelpi E, Beilharz M, Riedel D, Golenbock DT, Geyer M, Walter J, Latz E, Heneka MT. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature. 2017 Dec 20;552(7685):355-361.
Zimmer S, Grebe A, Bakke SS, Bode N, Halvorsen B, Ulas T, Skjelland M, De Nardo D, Labzin LI, Kerksiek A, Hempel C, Heneka MT, Hawxhurst V, Fitzgerald ML, Trebicka J, Björkhem I, Gustafsson JÅ, Westerterp M, Tall AR, Wright SD, Espevik T, Schultze JL, Nickenig G, Lütjohann D, Latz E. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Sci Transl Med. 2016 Apr 6;8(333):333ra50
Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, Brenker C, Nordhoff M, Mirandola SR, Al-Amoudi A, Mangan MS, Zimmer S, Monks BG, Fricke M, Schmidt RE, Espevik T, Jones B, Jarnicki AG, Hansbro PM, Busto P, Marshak-Rothstein A, Hornemann S, Aguzzi A, Kastenmüller W & Eicke Latz. The adaptor ASC has extracellular and ‘prionoid’ activities that propagate inflammation. Nat immunol, 2014, Aug;15(8):727-37
De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schilberg FA, Vogelhuber J, Kraut M, Ulas T, Kerksiek A, Krebs W, Bode N, Grebe A, Fitzgerald ML, Hernandez NJ, Williams B, Knolle PA, Kneiling M, Rocken M, Lutjohann D, Wright SD, Schultze JL, Latz E. HDL mediates anti-inflammatory transcriptional reprogramming of macrophages via ATF3. Nat Immunol, 2014 15(2), 152-160
Ablasser A, Schmid-Burgk JL, Hemmerling I, Horvath GL, Schmidt T, Latz E, Hornung V. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature. 2013 Nov 28;503(7477):530-4.
Heneka MT*, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, Gelpi E, Halle A, Korte M, Latz E* and Golenbock DT* (2013). NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. Jan 31;493(7434):674-8.
Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nunez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E (2010). NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464: 1357-61
Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E* & Fitzgerald KA*. (2009). AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature, 458(7237): 514-518. *shared last author
Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA, Latz E (2008). Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol 9: 847-56
Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT. (2008) The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol 9: 857-65
Latz E, Verma A, Visintin A, Gong M, Sirois CM, Klein DC, Monks BG, McKnight CJ, Lamphier MS, Duprex WP, Espevik T, Golenbock DT. (2007) Ligand-induced conformational changes allosterically activate Toll-like receptor 9. Nat Immunol 8: 772-9
Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT. (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5: 190-8
Selected Reviews:
Akbal A, Dernst A, Lovotti M, Mangan MSJ, McManus RM, Latz E. How location and cellular signaling combine to activate the NLRP3 inflammasome. Cell Mol Immunol. 2022 Nov;19(11):1201-1214.
Mihai G Netea, Jorge Domínguez-Andrés, Luis B Barreiro, Triantafyllos Chavakis, Maziar Divangahi, Elaine Fuchs, Leo AB Joosten, Jos WM van der Meer, Musa M Mhlanga, Willem JM Mulder, Niels P Riksen, Andreas Schlitzer, Joachim L Schultze, Christine Stabell Benn, Joseph C Sun, Ramnik J Xavier, Eicke Latz (2020). Defining trained immunity and its role in health and disease. Nature Reviews Immunology March 4;1-14
Anette Christ, Mario Lauterbach, Eicke Latz. Western Diet and the Immune System: An Inflammatory Connection. Immunity 2019 Nov 19, 51:794-811
Anette Christ, Eicke Latz. The Western lifestyle has lasting effects on metaflammation. Nature Reviews Immunology. 2019 Mai, 19;5: 267-268
Labzin LI, Heneka MT, Latz E. Innate Immunity and Neurodegeneration. Annu Rev Med. 2018 Jan 29;69:437-449.
Próchnicki T, Latz E. Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control. Cell Metab. 2017 Jul 5;26(1):71-93.
Netea MG, Balkwill F, Chonchol M, Cominelli F, Donath MY, Giamarellos-Bourboulis EJ, Golenbock D, Gresnigt MS, Heneka MT, Hoffman HM, Hotchkiss R, Joosten LAB, Kastner DL, Korte M, Latz E, Libby P, Mandrup-Poulsen T, Mantovani A, Mills KHG, Nowak KL, O’Neill LA, Pickkers P, van der Poll T, Ridker PM, Schalkwijk J, Schwartz DA, Siegmund B, Steer CJ, Tilg H, van der Meer JWM, van de Veerdonk FL, Dinarello CA. A guiding map for inflammation. Nat Immunol. 2017 Jul 19;18(8):826-831.
Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O’Neill LA, Xavier RJ. Trained immunity: A program of innate immune memory in health and disease. Science. 2016 Apr 22;352(6284)
Franklin BS, Mangan MS, Latz E. Crystal Formation in Inflammation. Annu Rev Immunol. 2016 Jan 11.
Heneka MT, Golenbock DT and Latz E. Innate immunity in Alzheimer’s disease. Nat Immunol, 2015 Mar;16(3):229-36.
Heneka MT, Kummer MP and Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014 Jul;14(7):463-77.
Broderick L, De Nardo D, Franklin BS, Hoffman HM, and Latz E. The Inflammasomes and Auto-inflammatory Syndromes. Annu Rev Pathol Mech Dis. 2015 Jan 24;10:395-424
Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013 Jun;13(6):397-411.
Hornung V and Latz E. 2010 Intracellular DNA recognition. Nat Rev Immunol. 10 (2): 123-130
