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Recent publications from Lang lab

Understanding the cellular basis of a Th1/Th17-inducing adjuvant

Desel, C., Murray PJ, Lehmann CHK, Heger L, Christensen D, Anderse P, Mack M, Dudziak D, Lang R. Monocytes elicit a neutrophil-independent Th1/Th17 response upon immunization with a Mincle-dependent glycolipid adjuvant, Frontiers in Immunology 2022, 13:880474; doi: 10.3389/fimmu.2022.880474. 2022

Development of subunit vaccines is hampered by a lack of adjuvants. The synthetic glycolipid TDB is a promising new adjuvant inducing protective Th1/Th17 immune responses via Mincle-Card9-dependent activation of antigen-presenting cells. The orchestration of Th1/Th17 induction by different innate immune cells is not well understood. Here, postdoctoral fellow Christiane Desel defined CCR2+ monocytes as the critical cell type for TDB-adjuvanticity, whereas neutrophils were dispensable. These findings provide a cellular mechanism for the generation of T cell responses, and furthermore suggest that unwanted side effects due to neutrophil activation may be dissociated from monocyte-elicited protective immunity.

Lack of miRNAs in DGCR8-deficiency does not block macrophage differentiation but causes overshooting type I IFN response to mycobacteria

Killy B, Bodendorfer B, Mages J, Ritter K, Schreiber J, Hölscher C, Pracht K, Ekici A, Jäck HM, Lang R. DGCR8 deficiency impairs macrophage growth and unleashes the interferon response to mycobacteria, Life Science Alliance 2021, 4 (6): e202000810.

MicroRNAs (miRNA) play an important role in regulation gene expression in innate immune cells and may be exploited by intracellular bacteria. In her PhD project, Barbara Killy addressed the question how a global abrogation of miRNA biosynthesis in DGCR8-deficient bone marrow cells affects the differentiation of macrophages and their interaction with the mycobacterial Mincle ligand TDM. Morphologically macrophages developed despite the lack of DGCR8, but were prone to overshooting type I interferon responses to TDM and to stimulation with whole bacteria of the Mycobacterium tuberculosis complex. Whether high IFNb expression in the absence of regulation by miRNA benefits the host or the mycobacteria will be interesting to explore in future studies.

Antagonism and synergy in the macrophage response to IFNg and the mycobacterial cord factor

Huber A et al. Mycobacterial cord factor reprograms the macrophage response to IFNg towards enhanced inflammation yet impaired antigen presentation and expression of GBP1. J Immunol August 12, 2020, ji2000337; DOI:

Trehalose-6,6-dimycolate (aka the cord factor) is the major PAMP of the mycobacterial cell wall and activates inflammatory cytokine production through MINCLE-CARD9 signaling. Alexandra Huber, Barbara Killy, Nadine Grummer and Barbara Bodendorfer, together with groups from Erlangen and Dresden show in this manuscript that cord factor signaling has ambiguous effects on the macrophage response to IFNg: while inflammatory cytokine and mediator production are enhanced, IFNg-induced MHC-II expression and induction of several GBPs is suppressed by the cord factor. This antagonism of IFNg-induced antigen presentation and anti-mycobacterial proteins may contribute to establish the intracellular niche of M. tuberculosis in its macrophage host.

TNF is essential for MINCLE expression: a new function for an old cytokine in innate immunity

Schick J et al. TNF is essential for mycobacteria-induced MINCLE expression, macrophage activation and Th17 adjuvanticity.

J Immunol (Cutting Edge) July 15, 2020, 205 (2) 323-328; DOI:

Several C-type lectin receptors (CLR) involved in the recognition of mycobacteria are upregulated on macrophages by microbial stimuli. The work by Judith Schick and colleagues from Erlangen, Munich, Düsseldorf, Borstel and Copenhagen now demonstrates that upregulation of the cord factor-receptor MINCLE in macrophages depends on the cytokine TNF. In vivo, deletion or pharmacologic blockade of TNF prevented Th17 adjuvanticity of the synthetic MINCLE ligand TDB. The findings implicate regulation of MINCLE and related CLR as a potential new mechanism in inhibition of resistance to mycobacteria and in vaccination responses by TNF blockade. The later will be further investigated in a PhD project in the new GRK 2599 (see for more information). 

Next Generation Sequencing enhances detection of bacteria in polymicrobial CNS infection

Stebner A et al., (2020) Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing, Clinical Microbiology and Infection,

Bacterial brain abscesses are severe infections requiring prolonged antibiotic treatment. Identification of bacteria present in brain abscesses is important for appropriate treatment but difficult with standard microbiological methods. In a collaboration with the Institute of Virology and the Department of Neurosurgery, Alexander Stebner tested the feasibility of Illumina MiSeq Next Generation Sequencing of 16S rDNA amplicons in a large set of samples from patients with brain abscess or bacterial meningitis. The majority of brain abscesses was indeed polymicrobial, with up to 16 different bacteria taxa detected per sample. The results published in Clinical Microbiology and Infection demonstrate that NGS expands the spectrum of bacteria detected in brain abscesses and is suitable for metagenomic diagnostics of this severe infection

Persistent infection with Coxiella burnetii in MyD88-knockout mice: a new mouse model for chronic Q fever

Kohl L, Hayek I, Daniel C, Schulze-Lührmann J, Bodendorfer B, Lührmann A and Lang R (2019) MyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination. Front. Immunol. 10:165. doi: 10.3389/fimmu.2019.00165

Infection with the zoonotic bacterium Coxiella burnetii is mostly self-limiting and resolves within several weeks, but becomes chronic and severe in some patients. To investigate the contribution of innate immune sensing mechanisms in the decision between resolution and chronicity, Lisa Kohl has used mice deficient in the central TLR adapter MyD88 in infection models with the attenuated Coxiella burnetii strain Nine Mile Phase II.  Strongly increased bacterial burden, that persisted in the lungs for at least 4 months after infection, show that TLR signaling is essential for early control of C. burnetii replication and to prevent persistent chronic infection. The study was performed in collaboration with the lab of Anja Lührmann and with Dr. Christoph Daniel (Department of Nephropathology).

Global profiling of cord factor-induced signaling and gene expression in macrophages

Hansen M, Peltier J, et al. (2019) Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and –independent Mycobacterial Cord Factor Signaling Molecular & Cellular Proteomics 18: 669–685, 2019. DOI: 10.1074/mcp. RA118.000929.

In a collaboration with Julien Peltier from the lab of Matthias Trost, Madlen Hansen performed the first quantitative phosphoproteome analysis of TDM-activated macrophages. Surprisingly, the bioinformatic results revealed Mincle-dependent and -independent phosphorylation, which appear to affect different biological processes. Whereas PI3K/AKT signaling, dependent on Mincle, is involved in TDM-induced cytokine regulation, Mincle-independent phosphorylation and transcriptomic changes were linked to cell cycle regulation. Collectively, the combined phosphoproteome and RNAseq datasets show substantial reprogramming of macrophages by TDM and reveal a dichotomy of MINCLE-dependent and -independent signaling linked to distinct biological responses.


  1. Stebner A, Ensser, A., Geissdoerfer, W., Bozhkov, Y., Lang, R. 2020. Molecular diagnosis of polymicrobial brain abscesses with 16S rDNA-based next generation sequencing. Clinical Microbiology and Infection accepted
  2. Schick J, Schafer J, Alexander C, Dichtl S, Murray PJ, Christensen D, Sorg U, Pfeffer K, Schleicher U, Lang R. 2020. Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17 Adjuvanticity. J Immunol 205: 323-8
  3. Huber A, Killy B, Grummel N, Bodendorfer B, Paul S, Wiesmann V, Naschberger E, Zimmer J, Wirtz S, Schleicher U, Vera J, Ekici AB, Dalpke A, Lang R. 2020. Mycobacterial Cord Factor Reprograms the Macrophage Response to IFN-gamma towards Enhanced Inflammation yet Impaired Antigen Presentation and Expression of GBP1. J Immunol 205: 1580-92
  4. Andreev D, Liu M, Weidner D, Kachler K, Faas M, Gruneboom A, Schlotzer-Schrehardt U, Munoz LE, Steffen U, Grotsch B, Killy B, Kronke G, Luebke AM, Niemeier A, Wehrhan F, Lang R, Schett G, Bozec A. 2020. Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin. J Clin Invest
  5. Weerasekera D, Fastner T, Lang R, Burkovski A, Ott L. 2019. Of mice and men: Interaction of Corynebacterium diphtheriae strains with murine and human phagocytes. Virulence 10: 414-28
  6. Pulido R, Lang R. 2019. Dual Specificity Phosphatases: From Molecular Mechanisms to Biological Function. Int J Mol Sci 20
  7. Moller J, Kraner M, Sonnewald U, Sangal V, Tittlbach H, Winkler J, Winkler TH, Melnikov V, Lang R, Sing A, Mattos-Guaraldi AL, Burkovski A. 2019. Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae. Vaccine 37: 3061-70
  8. Lepenies B, Lang R. 2019. Editorial: Lectins and Their Ligands in Shaping Immune Responses. Front Immunol 10: 2379
  9. Lang R, Raffi FAM. 2019. Dual-Specificity Phosphatases in Immunity and Infection: An Update. Int J Mol Sci 20
  10. Kohl L, Hayek I, Daniel C, Schulze-Luhrmann J, Bodendorfer B, Luhrmann A, Lang R. 2019. MyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination. Front Immunol 10: 165
  11. Hayek I, Fischer F, Schulze-Luehrmann J, Dettmer K, Sobotta K, Schatz V, Kohl L, Boden K, Lang R, Oefner PJ, Wirtz S, Jantsch J, Luhrmann A. 2019. Limitation of TCA Cycle Intermediates Represents an Oxygen-Independent Nutritional Antibacterial Effector Mechanism of Macrophages. Cell Rep 26: 3502-10 e6
  12. Hansen M, Peltier J, Killy B, Amin B, Bodendorfer B, Hartlova A, Uebel S, Bosmann M, Hofmann J, Buttner C, Ekici AB, Kuttke M, Franzyk H, Foged C, Beer-Hammer S, Schabbauer G, Trost M, Lang R. 2019. Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling. Mol Cell Proteomics 18: 669-85
  13. Spitzer P, Lang R, Oberstein TJ, Lewczuk P, Ermann N, Huttner HB, Masouris I, Kornhuber J, Kodel U, Maler JM. 2018. A Specific Reduction in Abeta1-42 vs. a Universal Loss of Abeta Peptides in CSF Differentiates Alzheimer's Disease From Meningitis and Multiple Sclerosis. Front Aging Neurosci 10: 152
  14. Patzelt T, Keppler SJ, Gorka O, Thoene S, Wartewig T, Reth M, Forster I, Lang R, Buchner M, Ruland J. 2018. Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells. Proc Natl Acad Sci U S A 115: 3120-5
  15. Benard A, Sakwa I, Schierloh P, Colom A, Mercier I, Tailleux L, Jouneau L, Boudinot P, Al-Saati T, Lang R, Rehwinkel J, Loxton AG, Kaufmann SHE, Anton-Leberre V, O'Garra A, Sasiain MDC, Gicquel B, Fillatreau S, Neyrolles O, Hudrisier D. 2018. B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis. Am J Respir Crit Care Med 197: 801-13
  16. Zega K, Jovanovic VM, Vitic Z, Niedzielska M, Knaapi L, Jukic MM, Partanen J, Friedel RF, Lang R, Brodski C. 2017. Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool. Front Mol Neurosci 10: 372
  17. Winterholler M, Coras R, Geissdorfer W, Rammensee R, Golitz P, Bogdan C, Lang R. 2017. Fatal Mycotic Aneurysm of the Basilar Artery Caused by Aspergillus fumigatus in a Patient with Pituitary Adenoma and Meningitis. Front Med (Lausanne) 4: 113
  18. Velasquez LN, Milillo MA, Delpino MV, Trotta A, Fernandez P, Pozner RG, Lang R, Balboa L, Giambartolomei GH, Barrionuevo P. 2017. Brucella abortus down-regulates MHC class II by the IL-6-dependent inhibition of CIITA through the downmodulation of IFN regulatory factor-1 (IRF-1). J Leukoc Biol 101: 759-73
  19. Tima HG, Al Dulayymi JR, Denis O, Lehebel P, Baols KS, Mohammed MO, L'Homme L, Sahb MM, Potemberg G, Legrand S, Lang R, Beyaert R, Piette J, Baird MS, Huygen K, Romano M. 2017. Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis. J Innate Immun 9: 162-80
  20. Steininger PA, Bobinger T, Dietrich W, Lee DH, Knott M, Bogdan C, Korn K, Lang R. 2017. Two Cases of Severe Tick-Borne Encephalitis in Rituximab-Treated Patients in Germany: Implications for Diagnosis and Prevention. Open Forum Infect Dis 4: ofx204
  21. Schmok E, Abad Dar M, Behrends J, Erdmann H, Ruckerl D, Endermann T, Heitmann L, Hessmann M, Yoshimura A, Rose-John S, Scheller J, Schaible UE, Ehlers S, Lang R, Holscher C. 2017. Suppressor of Cytokine Signaling 3 in Macrophages Prevents Exacerbated Interleukin-6-Dependent Arginase-1 Activity and Early Permissiveness to Experimental Tuberculosis. Front Immunol 8: 1537
  22. Schick J, Etschel P, Bailo R, Ott L, Bhatt A, Lepenies B, Kirschning C, Burkovski A, Lang R. 2017. Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids. Infect Immun 85
  23. Rath T, Atreya R, Geissdorfer W, Lang R, Nagel A, Neurath MF. 2017. A Severe Case of Tuberculosis Radiologically and Endoscopically Mimicking Colorectal Cancer with Peritoneal Carcinomatosis. Case Rep Gastrointest Med 2017: 6206951
  24. Patin EC, Geffken AC, Willcocks S, Leschczyk C, Haas A, Nimmerjahn F, Lang R, Ward TH, Schaible UE. 2017. Trehalose dimycolate interferes with FcgammaR-mediated phagosome maturation through Mincle, SHP-1 and FcgammaRIIB signalling. PLoS One 12: e0174973
  25. Ott L, Hacker E, Kunert T, Karrington I, Etschel P, Lang R, Wiesmann V, Wittenberg T, Singh A, Varela C, Bhatt A, Sangal V, Burkovski A. 2017. Analysis of Corynebacterium diphtheriae macrophage interaction: Dispensability of corynomycolic acids for inhibition of phagolysosome maturation and identification of a new gene involved in synthesis of the corynomycolic acid layer. PLoS One 12: e0180105
  26. Ostrop J, Lang R. 2017. Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors. J Immunol 198: 1403-14
  27. Lang R, Schick J. 2017. Review: Impact of Helminth Infection on Antimycobacterial Immunity-A Focus on the Macrophage. Front Immunol 8: 1864
  28. Lang R, Mattner J. 2017. The role of lipids in host microbe interactions. Front Biosci (Landmark Ed) 22: 1581-98
  29. Kao D, Lux A, Schaffert A, Lang R, Altmann F, Nimmerjahn F. 2017. IgG subclass and vaccination stimulus determine changes in antigen specific antibody glycosylation in mice. Eur J Immunol 47: 2070-9
  30. Jurkin J, Krump C, Koffel R, Fieber C, Schuster C, Brunner PM, Borek I, Eisenwort G, Lim C, Mages J, Lang R, Bauer W, Mechtcheriakova D, Meshcheryakova A, Elbe-Burger A, Stingl G, Strobl H. 2017. Human skin dendritic cell fate is differentially regulated by the monocyte identity factor Kruppel-like factor 4 during steady state and inflammation. J Allergy Clin Immunol 139: 1873-84 e10
  31. Spitzer P, Condic M, Herrmann M, Oberstein TJ, Scharin-Mehlmann M, Gilbert DF, Friedrich O, Gromer T, Kornhuber J, Lang R, Maler JM. 2016. Amyloidogenic amyloid-beta-peptide variants induce microbial agglutination and exert antimicrobial activity. Sci Rep 6: 32228
  32. Patin EC, Willcocks S, Orr S, Ward TH, Lang R, Schaible UE. 2016. Mincle-mediated anti-inflammatory IL-10 response counter-regulates IL-12 in vitro. Innate Immun 22: 181-5
  33. Patin EC, Jones AV, Thompson A, Clement M, Liao CT, Griffiths JS, Wallace LE, Bryant CE, Lang R, Rosenstiel P, Humphreys IR, Taylor PR, Jones GW, Orr SJ. 2016. IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-beta Production Inhibits Fungal Clearance. J Immunol 197: 208-21
  34. Maor-Nof M, Romi E, Shalom HS, Ulisse V, Raanan C, Nof A, Leshkowitz D, Lang R, Yaron A. 2016. Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors. Neuron 92: 991-1006
  35. Hupfer T, Schick J, Jozefowski K, Voehringer D, Ostrop J, Lang R. 2016. Stat6-Dependent Inhibition of Mincle Expression in Mouse and Human Antigen-Presenting Cells by the Th2 Cytokine IL-4. Front Immunol 7: 423
  36. Huber A, Kallerup RS, Korsholm KS, Franzyk H, Lepenies B, Christensen D, Foged C, Lang R. 2016. Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo. Innate Immun 22: 405-18
  37. Wenzel J, Ouderkirk JL, Krendel M, Lang R. 2015. Class I myosin Myo1e regulates TLR4-triggered macrophage spreading, chemokine release, and antigen presentation via MHC class II. Eur J Immunol 45: 225-37
  38. Siegert I, Schodel J, Nairz M, Schatz V, Dettmer K, Dick C, Kalucka J, Franke K, Ehrenschwender M, Schley G, Beneke A, Sutter J, Moll M, Hellerbrand C, Wielockx B, Katschinski DM, Lang R, Galy B, Hentze MW, Koivunen P, Oefner PJ, Bogdan C, Weiss G, Willam C, Jantsch J. 2015. Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia-Inducible Factor-1alpha upon LPS Activation in the Presence of Ample Oxygen. Cell Rep 13: 2048-55
  39. Rabes A, Zimmermann S, Reppe K, Lang R, Seeberger PH, Suttorp N, Witzenrath M, Lepenies B, Opitz B. 2015. The C-Type Lectin Receptor Mincle Binds to Streptococcus pneumoniae but Plays a Limited Role in the Anti-Pneumococcal Innate Immune Response. Plos One 10
  40. Ostrop J, Jozefowski K, Zimmermann S, Hofmann K, Strasser E, Lepenies B, Lang R. 2015. Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB. J Immunol 195: 2417-28
  41. Niedzielska M, Raffi FA, Tel J, Muench S, Jozefowski K, Alati N, Lahl K, Mages J, Billmeier U, Schiemann M, Appelt UK, Wirtz S, Sparwasser T, Hochrein H, Figdor CG, Keyse SM, Lang R. 2015. Selective Expression of the MAPK Phosphatase Dusp9/MKP-4 in Mouse Plasmacytoid Dendritic Cells and Regulation of IFN-beta Production. J Immunol 195: 1753-62
  42. Goldmann T, Zeller N, Raasch J, Kierdorf K, Frenzel K, Ketscher L, Basters A, Staszewski O, Brendecke SM, Spiess A, Tay TL, Kreutz C, Timmer J, Mancini GM, Blank T, Fritz G, Biber K, Lang R, Malo D, Merkler D, Heikenwalder M, Knobeloch KP, Prinz M. 2015. USP18 lack in microglia causes destructive interferonopathy of the mouse brain. EMBO J
  43. Schoenen H, Huber A, Sonda N, Zimmermann S, Jantsch J, Lepenies B, Bronte V, Lang R. 2014. Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPbeta and HIF1alpha. J Immunol 193: 3664-75
  44. Niedzielska M, Bodendorfer B, Munch S, Eichner A, Derigs M, da Costa O, Schweizer A, Neff F, Nitschke L, Sparwasser T, Keyse SM, Lang R. 2014. Gene trap mice reveal an essential function of dual specificity phosphatase Dusp16/MKP-7 in perinatal survival and regulation of Toll-like receptor (TLR)-induced cytokine production. J Biol Chem 289: 2112-26
  45. Goktuna SI, Canli O, Bollrath J, Fingerle AA, Horst D, Diamanti MA, Pallangyo C, Bennecke M, Nebelsiek T, Mankan AK, Lang R, Artis D, Hu Y, Patzelt T, Ruland J, Kirchner T, Taketo MM, Chariot A, Arkan MC, Greten FR. 2014. IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells. Cell Rep 7: 1914-25
  46. Globisch T, Steiner N, Fulle L, Lukacs-Kornek V, Degrandi D, Dresing P, Alferink J, Lang R, Pfeffer K, Beyer M, Weighardt H, Kurts C, Ulas T, Schultze JL, Forster I. 2014. Cytokine-dependent regulation of dendritic cell differentiation in the splenic microenvironment. Eur J Immunol 44: 500-10
  47. Friedrich O, Yi B, Edwards JN, Reischl B, Wirth-Hucking A, Buttgereit A, Lang R, Weber C, Polyak F, Liu I, von Wegner F, Cully TR, Lee A, Most P, Volkers M. 2014. IL-1alpha reversibly inhibits skeletal muscle ryanodine receptor. a novel mechanism for critical illness myopathy? Am J Respir Cell Mol Biol 50: 1096-106
  48. Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, Rupec RA, Gerhard M, Schmid R, Barker N, Clevers H, Lang R, Neumann J, Kirchner T, Taketo MM, van den Brink GR, Sansom OJ, Arkan MC, Greten FR. 2013. Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152: 25-38
  49. Puttur F, Arnold-Schrauf C, Lahl K, Solmaz G, Lindenberg M, Mayer CT, Gohmert M, Swallow M, van Helt C, Schmitt H, Nitschke L, Lambrecht BN, Lang R, Messerle M, Sparwasser T. 2013. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance. PLoS Pathog 9: e1003648
  50. Held C, Wenzel J, Wiesmann V, Palmisano R, Lang R, Wittenberg T. 2013. Enhancing automated micrograph-based evaluation of LPS-stimulated macrophage spreading. Cytometry A 83: 409-18
  51. Heitmann L, Schoenen H, Ehlers S, Lang R, Holscher C. 2013. Mincle is not essential for controlling Mycobacterium tuberculosis infection. Immunobiology 218: 506-16
  52. Desel C, Werninghaus K, Ritter M, Jozefowski K, Wenzel J, Russkamp N, Schleicher U, Christensen D, Wirtz S, Kirschning C, Agger EM, da Costa CP, Lang R. 2013. The Mincle-Activating Adjuvant TDB Induces MyD88-Dependent Th1 and Th17 Responses through IL-1R Signaling. Plos One 8
  53. Specht S, Taylor MD, Hoeve MA, Allen JE, Lang R, Hoerauf A. 2012. Over expression of IL-10 by macrophages overcomes resistance to murine filariasis. Exp Parasitol 132: 90-6
  54. Oeder S, Jorres RA, Weichenmeier I, Pusch G, Schober W, Pfab F, Behrendt H, Schierl R, Kronseder A, Nowak D, Dietrich S, Fernandez-Caldas E, Lintelmann J, Zimmermann R, Lang R, Mages J, Fromme H, Buters JT. 2012. Airborne indoor particles from schools are more toxic than outdoor particles. Am J Respir Cell Mol Biol 47: 575-82
  55. Frankenberger M, Hofer TP, Marei A, Dayyani F, Schewe S, Strasser C, Aldraihim A, Stanzel F, Lang R, Hoffmann R, Prazeres da Costa O, Buch T, Ziegler-Heitbrock L. 2012. Transcript profiling of CD16-positive monocytes reveals a unique molecular fingerprint. Eur J Immunol 42: 957-74
  56. Al Masalma M, Lonjon M, Richet H, Dufour H, Roche PH, Drancourt M, Raoult D, Fournier PE. 2012. Metagenomic analysis of brain abscesses identifies specific bacterial associations. Clin Infect Dis 54: 202-10
  57. Wenzel J, Held C, Palmisano R, Teufel S, David JP, Wittenberg T, Lang R. 2011. Measurement of TLR-Induced Macrophage Spreading by Automated Image Analysis: Differential Role of Myd88 and MAPK in Early and Late Responses. Front Physiol 2: 71
  58. Strebovsky J, Walker P, Lang R, Dalpke AH. 2011. Suppressor of cytokine signaling 1 (SOCS1) limits NF kappa B signaling by decreasing p65 stability within the cell nucleus. Faseb Journal 25: 863-74
  59. Lang R, Schoenen H, Desel C. 2011. Targeting Syk-Card9-activating C-type lectin receptors by vaccine adjuvants: findings, implications and open questions. Immunobiology 216: 1184-91
  60. Kratochvill F, Machacek C, Vogl C, Ebner F, Sedlyarov V, Gruber AR, Hartweger H, Vielnascher R, Karaghiosoff M, Rulicke T, Muller M, Hofacker I, Lang R, Kovarik P. 2011. Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation. Mol Syst Biol 7: 560
  61. Klotz C, Ziegler T, Figueiredo AS, Rausch S, Hepworth MR, Obsivac N, Sers C, Lang R, Hammerstein P, Lucius R, Hartmann S. 2011. A helminth immunomodulator exploits host signaling events to regulate cytokine production in macrophages. PLoS Pathog 7: e1001248
  62. Jantsch J, Wiese M, Schodel J, Castiglione K, Glasner J, Kolbe S, Mole D, Schleicher U, Eckardt KU, Hensel M, Lang R, Bogdan C, Schnare M, Willam C. 2011. Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1 alpha (HIF1A) and result in differential HIF1A-dependent gene expression. Journal of Leukocyte Biology 90: 551-62
  63. Held C, Wenzel J, Webel R, Marschall M, Lang R, Palmisano R, Wittenberg T. 2011. Using multimodal information for the segmentation of fluorescent micrographs with application to virology and microbiology. Conf Proc IEEE Eng Med Biol Soc 2011: 6487-90
  64. Weintz G, Olsen JV, Fruhauf K, Niedzielska M, Amit I, Jantsch J, Mages J, Frech C, Dolken L, Mann M, Lang R. 2010. The phosphoproteome of toll-like receptor-activated macrophages. Mol Syst Biol 6: 371
  65. Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger EM, Stenger S, Andersen P, Ruland J, Brown GD, Wells C, Lang R. 2010. Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. J Immunol 184: 2756-60
  66. Rodriguez N, Dietrich H, Mossbrugger I, Weintz G, Scheller J, Hammer M, Quintanilla-Martinez L, Rose-John S, Miethke T, Lang R. 2010. Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1(-/-) mice: critical role of IL-6. J Leukoc Biol 88: 579-87
  67. Layland LE, Mages J, Loddenkemper C, Hoerauf A, Wagner H, Lang R, da Costa CUP. 2010. Pronounced Phenotype in Activated Regulatory T Cells during a Chronic Helminth Infection. Journal of Immunology 184: 713-24
  68. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, Habenicht AJR, Ziegler-Heitbrock L, Randolph GJ. 2010. Comparison of gene expression profiles between human and mouse monocyte subsets. (vol 115, pg e10, 2010). Blood 116: 857-
  69. Hammer M, Echtenachter B, Weighardt H, Jozefowski K, Rose-John S, Mannel DN, Holzmann B, Lang R. 2010. Increased inflammation and lethality of Dusp1-/- mice in polymicrobial peritonitis models. Immunology 131: 395-404
  70. Werninghaus K, Babiak A, Gross O, Holscher C, Dietrich H, Agger EM, Mages J, Mocsai A, Schoenen H, Finger K, Nimmerjahn F, Brown GD, Kirschning C, Heit A, Andersen P, Wagner H, Ruland J, Lang R. 2009. Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation. J Exp Med 206: 89-97
  71. Schreiber T, Ehlers S, Heitmann L, Rausch A, Mages J, Murray PJ, Lang R, Holscher C. 2009. Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity. J Immunol 183: 1301-12
  72. Schaljo B, Kratochvill F, Gratz N, Sadzak I, Sauer I, Hammer M, Vogl C, Strobl B, Muller M, Blackshear PJ, Poli V, Lang R, Murray PJ, Kovarik P. 2009. Tristetraprolin is required for full anti-inflammatory response of murine macrophages to IL-10. J Immunol 183: 1197-206
  73. Renstrom J, Istvanffy R, Gauthier K, Shimono A, Mages J, Jardon-Alvarez A, Kroger M, Schiemann M, Busch DH, Esposito I, Lang R, Peschel C, Oostendorp RA. 2009. Secreted frizzled-related protein 1 extrinsically regulates cycling activity and maintenance of hematopoietic stem cells. Cell Stem Cell 5: 157-67
  74. Rad R, Ballhorn W, Voland P, Eisenacher K, Mages J, Rad L, Ferstl R, Lang R, Wagner H, Schmid RM, Bauer S, Prinz C, Kirschning CJ, Krug A. 2009. Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori. Gastroenterology 136: 2247-57
  75. Hertle ML, Popp C, Petermann S, Maier S, Kremmer E, Lang R, Mages J, Kempkes B. 2009. Differential gene expression patterns of EBV infected EBNA-3A positive and negative human B lymphocytes. PLoS Pathog 5: e1000506
  76. Andersen CA, Rosenkrands I, Olsen AW, Nordly P, Christensen D, Lang R, Kirschning C, Gomes JM, Bhowruth V, Minnikin DE, Besra GS, Follmann F, Andersen P, Agger EM. 2009. Novel generation mycobacterial adjuvant based on liposome-encapsulated monomycoloyl glycerol from Mycobacterium bovis bacillus Calmette-Guerin. J Immunol 183: 2294-302
  77. Aly S, Mages J, Reiling N, Kalinke U, Decker T, Lang R, Ehlers S. 2009. Mycobacteria-induced granuloma necrosis depends on IRF-1. Journal of Cellular and Molecular Medicine 13: 2069-82
  78. von Burstin J, Eser S, Seidler B, Meining A, Bajbouj M, Mages J, Lang R, Kind AJ, Schnieke AE, Schmid RM, Schneider G, Saur D. 2008. Highly sensitive detection of early-stage pancreatic cancer by multimodal near-infrared molecular imaging in living mice. International Journal of Cancer 123: 2138-47
  79. Rodriguez N, Lang R, Wantia N, Cirl C, Ertl T, Durr S, Wagner H, Miethke T. 2008. Induction of iNOS by Chlamydophila pneumoniae requires MyD88-dependent activation of JNK. Journal of Leukocyte Biology 84: 1585-93
  80. Prinz M, Schmidt H, Mildner A, Knobeloch KP, Hanisch UK, Raasch J, Merkler D, Detje C, Gutcher I, Mages J, Lang R, Martin R, Gold R, Becher B, Bruck W, Kalinke U. 2008. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system. Immunity 28: 675-86
  81. Mages J, Freimuller K, Lang R, Hatzopoulos AK, Guggemoos S, Koszinowski UH, Adler H. 2008. Proteins of the secretory pathway govern virus productivity during lytic gammaherpesvirus infection. Journal of Cellular and Molecular Medicine 12: 1974-89
  82. Ledran MH, Krassowska A, Armstrong L, Dimmick I, Renstrom J, Lang R, Yung S, Santibanez-Coref M, Dzierzak E, Stojkovic M, Oostendorp RAJ, Forrester L, Lako M. 2008. Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell 3: 85-98
  83. Kalali BN, Kollisch G, Mages J, Muller T, Bauer S, Wagner H, Ring J, Lang R, Mempel M, Ollert M. 2008. Double-stranded RNA induces an antiviral defense status in epidermal keratinocytes through TLR3-, PKR-, and MDA5/RIG-I-mediated differential signaling. J Immunol 181: 2694-704
  84. Hofer TPJ, Frankenberger M, Mages J, Lang R, Hoffmann R, Colige A, Ziegler-Heitbrock L. 2008. Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids. Journal of Molecular Medicine-Jmm 86: 323-32
  85. Farhat K, Riekenberg S, Heine H, Debarry J, Lang R, Mages J, Buwitt-Beckmann U, Roeschmann K, Jung G, Wiesmuller KH, Ulmer AJ. 2008. Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. Journal of Leukocyte Biology 83: 692-701
  86. Eckmann L, Nebelsiek T, Fingerle AA, Dann SM, Mages J, Lang R, Robine S, Kagnoff MF, Schmid RM, Karin M, Arkan MC, Greten FR. 2008. Opposing functions of IKK beta during acute and chronic intestinal inflammation. Proceedings of the National Academy of Sciences of the United States of America 105: 15058-63
  87. Agger EM, Rosenkrands I, Hansen J, Brahimi K, Vandahl BS, Aagaard C, Werninghaus K, Kirschning C, Lang R, Christensen D, Theisen M, Follmann F, Andersen P. 2008. Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01): a versatile adjuvant for vaccines with different immunological requirements. PLoS One 3: e3116
  88. Schmitz F, Heit A, Guggemoos S, Krug A, Mages J, Schiemann M, Adler H, Drexler I, Haas T, Lang R, Wagner H. 2007. Interferon-regulatory-factor 1 controls Toll-like receptor 9-mediated IFN-beta production in myeloid dendritic cells. Eur J Immunol 37: 315-27
  89. Rodriguez N, Mages J, Dietrich H, Wantia N, Wagner H, Lang R, Miethke T. 2007. MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae. Physiol Genomics 30: 134-45
  90. Rad R, Brenner L, Krug A, Voland P, Mages J, Lang R, Schwendy S, Reindl W, Dossumbekova A, Ballhorn W, Wagner H, Schmid RM, Bauer S, Prinz C. 2007. Toll-like receptor-dependent activation of antigen-presenting cells affects adaptive immunity to Helicobacter pylori. Gastroenterology 133: 150-63 e3
  91. Oeder S, Mages J, Flicek P, Lang R. 2007. Uncovering information on expression of natural antisense transcripts in Affymetrix MOE430 datasets. BMC Genomics 8: 200
  92. Mayer AK, Muehmer M, Mages J, Gueinzius K, Hess C, Heeg K, Bals R, Lang R, Dalpke AH. 2007. Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells. J Immunol 178: 3134-42
  93. Mages J, Dietrich H, Lang R. 2007. A genome-wide analysis of LPS tolerance in macrophages. Immunobiology 212: 723-37
  94. Aly S, Laskay T, Mages J, Malzan A, Lang R, Ehlers S. 2007. Interferon-gamma-dependent mechanisms of mycobacteria-induced pulmonary immunopathology: the role of angiostasis and CXCR3-targeted chemokines for granuloma necrosis. J Pathol 212: 295-305
  95. Weighardt H, Mages J, Jusek G, Kaiser-Moore S, Lang R, Holzmann B. 2006. Organ-specific role of MyD88 for gene regulation during polymicrobial peritonitis. Infect Immun 74: 3618-32
  96. Maier S, Staffler G, Hartmann A, Hock J, Henning K, Grabusic K, Mailhammer R, Hoffmann R, Wilmanns M, Lang R, Mages J, Kempkes B. 2006. Cellular target genes of Epstein-Barr virus nuclear antigen 2. Journal of Virology 80: 9761-71
  97. Lang R, Hammer M, Mages J. 2006. DUSP meet immunology: dual specificity MAPK phosphatases in control of the inflammatory response. J Immunol 177: 7497-504
  98. Keller C, Hoffmann R, Lang R, Brandau S, Hermann C, Ehlers S. 2006. Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect Immun 74: 4295-309
  99. Hammer M, Mages J, Dietrich H, Servatius A, Howells N, Cato AC, Lang R. 2006. Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock. J Exp Med 203: 15-20
  100. Dossumbekova A, Prinz C, Mages J, Lang R, Kusters JG, Van Vliet AHM, Reindl W, Backert S, Saur D, Schmid RM, Rad R. 2006. Helicobacter pylori HopH (OipA) and bacterial pathogenicity: Genetic and functional genomic analysis of hopH gene Polymorphisms. Journal of Infectious Diseases 194: 1346-55
  101. Ludwig H, Mages J, Staib C, Lehmann MH, Lang R, Sutter G. 2005. Role of viral factor E3L in modified vaccinia virus Ankara infection of human HeLa cells: Regulation of the virus life cycle and identification of differentially expressed host genes. Journal of Virology 79: 2584-96
  102. Lang R. 2005. Tuning of macrophage responses by Stat3-inducing cytokines: molecular mechanisms and consequences in infection. Immunobiology 210: 63-76
  103. Hammer M, Mages J, Dietrich H, Schmitz F, Striebel F, Murray PJ, Wagner H, Lang R. 2005. Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. Eur J Immunol 35: 2991-3001
  104. Weighardt H, Jusek G, Mages J, Lang R, Hoebe K, Beutler B, Holzmann B. 2004. Identification of a TLR4- and TRIF-dependent activation program of dendritic cells. European Journal of Immunology 34: 558-64
  105. Schmitz F, Mages J, Heit A, Lang R, Wagner H. 2004. Transcriptional activation induced in macrophages by Toll-like receptor (TLR) ligands: from expression profiling to a model of TLR signaling. Eur J Immunol 34: 2863-73
  106. Rad R, Dossumbekova A, Neu B, Lang R, Bauer S, Saur D, Gerhard M, Prinz C. 2004. Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection. Gut 53: 1082-9
  107. Pauleau AL, Rutschman R, Lang R, Pernis A, Watowich SS, Murray PJ. 2004. Enhancer-mediated control of macrophage-specific arginase I expression. J Immunol 172: 7565-73
  108. Lang R, Pauleau AL, Parganas E, Takahashi Y, Mages J, Ihle JN, Rutschman R, Murray PJ. 2003. SOCS3 regulates the plasticity of gp130 signaling. Nat Immunol 4: 546-50
  109. Rad R, Gerhard M, Lang R, Schoniger M, Rosch T, Schepp W, Becker I, Wagner H, Prinz C. 2002. The Helicobacter pylori blood group antigen-binding adhesin facilitates bacterial colonization and augments a nonspecific immune response. Journal of Immunology 168: 3033-41
  110. Lang R, Rutschman RL, Greaves DR, Murray PJ. 2002. Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter. J Immunol 168: 3402-11
  111. Lang R, Patel D, Morris JJ, Rutschman RL, Murray PJ. 2002. Shaping gene expression in activated and resting primary macrophages by IL-10. J Immunol 169: 2253-63
  112. Kornhuber ME, Ganz C, Lang R, Brill T, Schmahl W. 2002. Focal encephalitis in the Lewis rat induced by intracerebral enterotoxin superantigen and amplified by activated intravenous splenocytes. Neuroscience Letters 324: 93-6
  113. Rutschman R, Lang R, Hesse M, Ihle JN, Wynn TA, Murray PJ. 2001. Cutting edge: Stat6-dependent substrate depletion regulates nitric oxide production. J Immunol 166: 2173-7
  114. Kranzer K, Bauer M, Lipford GB, Heeg K, Wagner H, Lang R. 2000. CpG-oligodeoxynucleotides enhance T-cell receptor-triggered interferon-gamma production and up-regulation of CD69 via induction of antigen-presenting cell-derived interferon type I and interleukin-12. Immunology 99: 170-8
  115. Lang R, Hultner L, Lipford GB, Wagner H, Heeg K. 1999. Guanosine-rich oligodeoxynucleotides induce proliferation of macrophage progenitors in cultures of murine bone marrow cells. European Journal of Immunology 29: 3496-506
  116. Lang R, Heeg K. 1998. Semiquantitative determination of human cytokine mRna expression using TaqMan RT-PCR. Inflammopharmacology 6: 297-309
  117. Lang R, Pfeffer K, Wagner H, Heeg K. 1997. A rapid method for semiquantitative analysis of the human V beta-repertoire using TaqMan(R) PCR. Journal of Immunological Methods 203: 181-92
  118. Lang R, Wagner H, Heeg K. 1995. Differential-Effects of the Immunosuppressive Agents Cyclosporine and Leflunomide in-Vivo - Leflunomide Blocks Clonal T-Cell Expansion yet Allows Production of Lymphokines and Manifestation of T-Cell-Mediated Shock. Transplantation 59: 382-9