How can we fight lung infections?

What is this research project about?

Fluorescence image of macrophages from genetically modified stem cells (iPSC).
Copyright: Shifaa Abdin

What is this research project about?

Within our research, we are focusing on infections of the lower respiratory tract such as pneumonia, which is still the most communicable disease worldwide. Our research aims to understand the onset of infectious diseases and to establish new therapeutic options based on approaches using regenerative medicine. In our research we use cells from patients, to establish new infection models, which will pave the way for cell-based immunotherapeutic approaches targeting infections of the lower respiratory tract. Our focus is primarily on the macrophages (phagocytes) of the immune system.

What’s the current status?

We have been successful in establishing a plethora of different infection models for bacteria and viruses. Based on this knowledge, we could also achieve the use of newly designed immune cells to combat life-threatening pulmonary infections. As of now, we are aiming to push these findings into the clinics. In particular, we are investigating the role of macrophages (scavenger cells) in the development of and fight against infections. We are using different types of stem cells for this purpose. One of our approaches is to replace the weakened phagocytes with healthy phagocytes from the laboratory, which then offer protection against bacteria or viruses.

Macrophages freshly derived from differentiation cultures of human stem cells (iPSC).
Copyright: Dr. Mania Ackermann

What are the project goals?

Our goals are new immunotherapeutic approaches using either designer immune cells or other immunotherapeutic approaches to combat pulmonary infections. We are focusing primarily on bacterial infections, with the long-term goal to use established systems also for viral intruders.

How do we get there?

In order to gain insights into the development of lung diseases and to be able to derive therapies from them, we establish different disease models in the laboratory. To do this, we are working in a highly inter-disciplinary environment, in which we combine several disciplines such as infection and regenerative medicine, stem cells and immunity. We are using the framework of RESIST to combine medical scientist with clinician scientist, to pave the development of new innovations and radical new ideas to combat bacterial pneumonia.

The figure shows the development of novel cell culture infection models with patient-specific iPSC immune cells.

Projectleader Prof. Lachmann

Project title: Control of Airway Infections

Nico Lachmann

Prof. Dr. Nico Lachmann

Projekt: B13

Publications of the Project B13

Publications 2023

Human IRF1 governs macrophagic IFN-Îł immunity to mycobacteria. Rosain J, Neehus AL, Manry J, Yang R, Le Pen J, Daher W, Liu Z, Chan YH, Tahuil N, TĂŒrel Ö, Bourgey M, Ogishi M, Doisne JM, Izquierdo HM, Shirasaki T, Le Voyer T, GuĂ©rin A, Bastard P, Moncada-VĂ©lez M, Han JE, Khan T, Rapaport F, Hong SH, Cheung A, Haake K, Mindt BC, PĂ©rez L, Philippot Q, Lee D, Zhang P, Rinchai D, Al Ali F, Ahmad Ata MM, Rahman M, Peel JN, Heissel S, Molina H, Kendir-Demirkol Y, Bailey R, Zhao S, Bohlen J, Mancini M, Seeleuthner Y, Roelens M, Lorenzo L, SoudĂ©e C, Paz MEJ, GonzĂĄlez ML, Jeljeli M, Soulier J, Romana S, L’Honneur AS, Materna M, MartĂ­nez-Barricarte R, Pochon M, Oleaga-Quintas C, Michev A, Migaud M, LĂ©vy R, Alyanakian MA, Rozenberg F, Croft CA, Vogt G, Emile JF, Kremer L, Ma CS, Fritz JH, Lemon SM, Spaan AN, Manel N, Abel L, MacDonald MR, Boisson-Dupuis S, Marr N, Tangye SG, Di Santo JP, Zhang Q, Zhang SY, Rice CM, BĂ©ziat V, Lachmann N, Langlais D, Casanova JL, Gros P, Bustamante J. Cell. 2023 Feb 2;186(3):621-645.e33. doi: 10.1016/j.cell.2022.12.038. PMID: 36736301; PMCID: PMC9907019.

Metabolic rewiring tunes dermal macrophages in staphylococcal skin infection. Sci Immunol. Forde AJ, Kolter J, Zwicky P, Baasch S, Lohrmann F, Eckert M, Gres V, Lagies S, Gorka O, Rambold AS, Buescher JM, Kammerer B, Lachmann N, Prinz M, Groß O, Pearce EJ, Becher B, Henneke P.  2023 Aug 18;8(86):eadg3517.

Adaptation of Human iPSC-Derived Macrophages Toward an Alveolar Macrophage-Like Phenotype Post-Intra-Pulmonary Transfer into Murine Models. Hetzel M, Gensch I, Ackermann M, Lachmann N.  Methods Mol Biol. 2024;2713:463-479.

Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting. Malainou C, Abdin SM, Lachmann N, Matt U, Herold S. J Clin Invest. 2023 Oct 2;133(19):e170501. doi: 10.1172/JCI170501. PMID: 37781922; PMCID: PMC10541196.

Scalable generation of functional human iPSC-derived CAR-macrophages that efficiently eradicate CD19-positive leukemia. Abdin SM, Paasch D, Kloos A, Oliveira MC, Jang MS, Ackermann M, Stamopoulou A, Mroch PJ, Falk CS, von Kaisenberg CS, Schambach A, Heuser M, Moritz T, Hansen G, Morgan M, Lachmann N.  J Immunother Cancer. 2023 Dec 22;11(12):e007705. doi: 10.1136/jitc-2023-007705. PMID: 38135346; PMCID: PMC10749073.

Publications 2022

Generation of Human iPSC from Small Volume Peripheral Blood Samples. Kloos D, Lachmann N. Methods Mol Biol. 2022;2429:27-39. doi: 10.1007/978-1-0716-1979-7_3. PMID: 35507153

ISG15 deficiency features a complex cellular phenotype that responds to treatment with itaconate and derivatives. Waqas SF, Sohail A, Nguyen AHH, Usman A, Ludwig T, Wegner A, Malik MNH, Schuchardt S, Geffers R, Winterhoff M, Merkert S, Martin U, Olmer R, Lachmann N, Pessler F. Clin Transl Med. 2022

Targeted biallelic integration of an inducible Caspase 9 suicide gene in iPSCs for safer therapies. Wunderlich S, Haase A, Merkert S, Jahn K, Deest M, Frieling H, Glage S, Korte W, Martens A, Kirschning A, Zeug A, Ponimaskin E, Göhring G, Ackermann M, Lachmann N, Moritz T, Zweigerdt R, Martin U. Mol Ther Methods Clin Dev.

Continuous human iPSC-macrophage mass production by suspension culture in stirred tank bioreactors. Ackermann M, Rafiei Hashtchin A, Manstein F, Carvalho Oliveira M, Kempf H, Zweigerdt R, Lachmann N. Nat Protoc. 2022 Jan 17.

Publications 2021

Beyond „Big Eaters“: The Versatile Role of Alveolar Macrophages in Health and Disease. Hetzel M, Ackermann M, Lachmann N. Int J Mol Sci. 2021 Mar 24;22(7):3308. doi: 10.3390/ijms22073308. PMID: 33804918 Free PMC article. Review.

Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model. Rafiei Hashtchin A, Fehlhaber B, Hetzel M, Manstein F, Stalp JL, Glage S, Abeln M, Zweigerdt R, Munder A, Viemann D, Ackermann M, Lachmann N. Blood Adv. 2021 Dec 14;5(23):5190-5201.

CARs and beyond: tailoring macrophage-based cell therapeutics to combat solid malignancies. Abdin SM, Paasch D, Morgan M, Lachmann N. J Immunother Cancer. 2021 Aug;9(8):e002741. doi: 10.1136/jitc-2021-002741. PMID: 34462325; PMCID: PMC8407221.

Genetic Correction of IL-10RB Deficiency Reconstitutes Anti-Inflammatory Regulation in iPSC-Derived Macrophages. Hoffmann D, Sens J, Brennig S, Brand D, Philipp F, Vollmer Barbosa P, Kuehle J, Steinemann D, Lenz D, Buchegger T, Morgan M, Falk CS, Klein C, Lachmann N, Schambach A.  J Pers Med. 2021 Mar 20;11(3):221. doi: 10.3390/jpm11030221. PMID: 33804706; PMCID: PMC8003874.

Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease. Ricke-Hoch M, Stelling E, Lasswitz L, Gunesch AP, Kasten M, Zapatero-BelinchĂłn FJ, Brogden G, Gerold G, Pietschmann T, Montiel V, Balligand JL, Facciotti F, Hirsch E, Gausepohl T, Elbahesh H, Rimmelzwaan GF, Höfer A, KĂŒhnel MP, Jonigk D, Eigendorf J, Tegtbur U, Mink L, Scherr M, Illig T, Schambach A, Pfeffer TJ, Hilfiker A, Haverich A, Hilfiker-Kleiner D.  PLoS One. 2021 Aug 4;16(8):e0255335. doi: 10.1371/journal.pone.0255335. PMID: 34347801; PMCID: PMC8336874.

iPS Cell-Based Model for MAPT Haplotype as a Risk Factor for Human Tauopathies Identifies No Major Differences in TAU Expression. Strauß T, Marvian-Tayaranian A, Sadikoglou E, Dhingra A, Wegner F, TrĂŒmbach D, Wurst W, Heutink P, Schwarz SC, Höglinger GU. Front Cell Dev Biol. 2021 Aug 31;9:726866. doi: 10.3389/fcell.2021.726866. PMID: 34532319; PMCID: PMC8438159.

Publications of the Project B13