Neutrophil extracellular traps characterize caseating granulomas.


Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
31 Jul 2024
Historique:
received: 20 12 2023
accepted: 04 07 2024
revised: 27 06 2024
medline: 1 8 2024
pubmed: 1 8 2024
entrez: 31 7 2024
Statut: epublish

Résumé

Tuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO-DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.

Identifiants

pubmed: 39085192
doi: 10.1038/s41419-024-06892-3
pii: 10.1038/s41419-024-06892-3
doi:

Substances chimiques

Cell-Free Nucleic Acids 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

548

Subventions

Organisme : China Scholarship Council (CSC)
ID : 202006370030
Organisme : Volkswagen Foundation (VolkswagenStiftung)
ID : Grant 97744
Organisme : Volkswagen Foundation (VolkswagenStiftung)
ID : Grant 97744
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 2886 PANDORA Project-No. B3
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CRC1181-261193037 (C03)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB/TRR 241 (B04)

Informations de copyright

© 2024. The Author(s).

Références

Fogel N. Tuberculosis: a disease without boundaries. Tuberculosis. 2015;95:527–31.
pubmed: 26198113 doi: 10.1016/j.tube.2015.05.017
Dudnyk A, Butov D, Crudu V, Lange C, Chesov D. MDR-TB in Eastern Europe in the era of the TB elimination action framework. Int J Tuberc Lung Dis. 2017;21:2–3.
pubmed: 28157456 doi: 10.5588/ijtld.16.0732
Chesov D, Butov D, Reimann M, Heyckendorf J, Myasoedov V, Butov T, et al. Impact of lung function on treatment outcome in patients with TB. Int J Tuberc Lung Dis. 2021;25:277–84.
pubmed: 33762071 doi: 10.5588/ijtld.20.0949
Seung KJ, Keshavjee S, Rich ML. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb Perspect Med. 2015;5:a017863.
pubmed: 25918181 pmcid: 4561400 doi: 10.1101/cshperspect.a017863
Kurz SG, Furin JJ, Bark CM. Drug-resistant tuberculosis: challenges and progress. Infect Dis Clin North Am. 2016;30:509–22.
pubmed: 27208770 pmcid: 4876017 doi: 10.1016/j.idc.2016.02.010
Polena H, Boudou F, Tilleul S, Dubois-Colas N, Lecointe C, Rakotosamimanana N, et al. Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination. Sci Rep. 2016;6:33162.
pubmed: 27616470 pmcid: 5018821 doi: 10.1038/srep33162
Cavalcante-Silva LHA, Almeida FS, Andrade AG, Comberlang FC, Cardoso LL, Vanderley SER, et al. Mycobacterium tuberculosis in a trap: the role of neutrophil extracellular traps in tuberculosis. Int J Mol Sci. 2023;24:11385.
Ravimohan S, Kornfeld H, Weissman D, Bisson GP. Tuberculosis and lung damage: from epidemiology to pathophysiology. Eur Respir Rev. 2018;27:170077.
pubmed: 29491034 pmcid: 6019552 doi: 10.1183/16000617.0077-2017
Huang L, Russell DG. Protective immunity against tuberculosis: what does it look like and how do we find it? Curr Opin Immunol. 2017;48:44–50.
pubmed: 28826036 pmcid: 5697896 doi: 10.1016/j.coi.2017.08.001
Young C, Walzl G, Du Plessis N. Therapeutic host-directed strategies to improve outcome in tuberculosis. Mucosal Immunol. 2020;13:190–204.
pubmed: 31772320 doi: 10.1038/s41385-019-0226-5
van der Meer AJ, Zeerleder S, Blok DC, Kager LM, Lede IO, Rahman W, et al. Neutrophil extracellular traps in patients with pulmonary tuberculosis. Respir Res. 2017;18:181.
pubmed: 29084563 pmcid: 5663039 doi: 10.1186/s12931-017-0663-1
Braian C, Hogea V, Stendahl O. Mycobacterium tuberculosis-induced neutrophil extracellular traps activate human macrophages. J Innate Immun. 2013;5:591–602.
pubmed: 23635526 pmcid: 6741595 doi: 10.1159/000348676
Ramos-Kichik V, Mondragon-Flores R, Mondragon-Castelan M, Gonzalez-Pozos S, Muniz-Hernandez S, Rojas-Espinosa O, et al. Neutrophil extracellular traps are induced by Mycobacterium tuberculosis. Tuberculosis. 2009;89:29–37.
pubmed: 19056316 doi: 10.1016/j.tube.2008.09.009
Hilda JN, Das S, Tripathy SP, Hanna LE. Role of neutrophils in tuberculosis: a bird’s eye view. Innate Immun. 2020;26:240–7.
pubmed: 31735099 doi: 10.1177/1753425919881176
Corleis B, Korbel D, Wilson R, Bylund J, Chee R, Schaible UE. Escape of Mycobacterium tuberculosis from oxidative killing by neutrophils. Cell Microbiol. 2012;14:1109–21.
pubmed: 22405091 doi: 10.1111/j.1462-5822.2012.01783.x
Dallenga T, Repnik U, Corleis B, Eich J, Reimer R, Griffiths GW, et al. M. tuberculosis-induced necrosis of infected neutrophils promotes bacterial growth following phagocytosis by macrophages. Cell Host Microbe. 2017;22:519–30.e3.
pubmed: 29024644 doi: 10.1016/j.chom.2017.09.003
Knopf J, Leppkes M, Schett G, Herrmann M, Munoz LE. Aggregated NETs sequester and detoxify extracellular histones. Front Immunol. 2019;10:2176.
pubmed: 31572386 pmcid: 6749074 doi: 10.3389/fimmu.2019.02176
Song Y, Kadiyala U, Weerappuli P, Valdez JJ, Yalavarthi S, Louttit C, et al. Antimicrobial microwebs of DNA-histone inspired from neutrophil extracellular traps. Adv Mater. 2019;31:e1807436.
pubmed: 30698844 pmcid: 6467213 doi: 10.1002/adma.201807436
Knopf J, Mahajan A, Munoz LE, Herrmann M. Formation and clearance of NETs in Health and disease. Cells. 2022;11:4022.
Zlatar L, Timm T, Lochnit G, Bilyy R, Bauerle T, Munoz-Becerra M, et al. Neutrophil extracellular traps drive dacryolithiasis. Cells. 2023;12:1857.
Schauer C, Janko C, Munoz LE, Zhao Y, Kienhofer D, Frey B, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20:511–7.
pubmed: 24784231 doi: 10.1038/nm.3547
Bilyy R, Fedorov V, Vovk V, Leppkes M, Dumych T, Chopyak V, et al. Neutrophil extracellular traps form a barrier between necrotic and viable areas in acute abdominal inflammation. Front Immunol. 2016;7:424.
pubmed: 27777576 pmcid: 5056318 doi: 10.3389/fimmu.2016.00424
Repasy T, Lee J, Marino S, Martinez N, Kirschner DE, Hendricks G, et al. Intracellular bacillary burden reflects a burst size for Mycobacterium tuberculosis in vivo. PLoS Pathog. 2013;9:e1003190.
pubmed: 23436998 pmcid: 3578792 doi: 10.1371/journal.ppat.1003190
Su R, Peng YP, Deng Z, Deng YT, Ye JQ, Guo Y, et al. Mycobacterium tuberculosis infection induces low-density granulocyte generation by promoting neutrophil extracellular trap formation via ROS pathway. Front Microbiol. 2019;10:1468.
pubmed: 31354639 pmcid: 6637951 doi: 10.3389/fmicb.2019.01468
de Melo MGM, Mesquita EDD, Oliveira MM, da Silva-Monteiro C, Silveira AKA, et al. Imbalance of NET and Alpha-1-antitrypsin in tuberculosis patients is related with hyper inflammation and severe lung tissue damage. Front Immunol. 2018;9:3147.
pubmed: 30687336 doi: 10.3389/fimmu.2018.03147
Porto BN, Stein RT. Neutrophil extracellular traps in pulmonary diseases: too much of a good thing? Front Immunol. 2016;7:311.
pubmed: 27574522 pmcid: 4983612 doi: 10.3389/fimmu.2016.00311
Singh J, Boettcher M, Dolling M, Heuer A, Hohberger B, Leppkes M, et al. Moonlighting chromatin: when DNA escapes nuclear control. Cell Death Differ. 2023;30:861–75.
pubmed: 36755071 pmcid: 9907214 doi: 10.1038/s41418-023-01124-1
Lin PL, Flynn JL. The end of the binary era: revisiting the spectrum of tuberculosis. J Immunol. 2018;201:2541–8.
pubmed: 30348659 doi: 10.4049/jimmunol.1800993
Muefong CN, Sutherland JS. Neutrophils in tuberculosis-associated inflammation and lung pathology. Front Immunol. 2020;11:962.
pubmed: 32536917 pmcid: 7266980 doi: 10.3389/fimmu.2020.00962
Alcantara CA, Glassman I, Nguyen KH, Parthasarathy A, Venketaraman V. Neutrophils in Mycobacterium tuberculosis. Vaccines. 2023;11:631.
Agrawal R, Kee AR, Ang L, Tun Hang Y, Gupta V, Kon OM, et al. Tuberculosis or sarcoidosis: opposite ends of the same disease spectrum? Tuberculosis. 2016;98:21–6.
pubmed: 27156614 doi: 10.1016/j.tube.2016.01.003
Marakalala MJ, Raju RM, Sharma K, Zhang YJ, Eugenin EA, Prideaux B, et al. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat Med. 2016;22:531–8.
pubmed: 27043495 pmcid: 4860068 doi: 10.1038/nm.4073
Rao M, Ippolito G, Mfinanga S, Ntoumi F, Yeboah-Manu D, Vilaplana C, et al. Latent TB infection (LTBI)—Mycobacterium tuberculosis pathogenesis and the dynamics of the granuloma battleground. Int J Infect Dis. 2019;80S:S58–S61.
pubmed: 30822547 doi: 10.1016/j.ijid.2019.02.035
Drake WP, Newman LS. Mycobacterial antigens may be important in sarcoidosis pathogenesis. Curr Opin Pulm Med. 2006;12:359–63.
pubmed: 16926652 doi: 10.1097/01.mcp.0000239554.01068.94
Seve P, Pacheco Y, Durupt F, Jamilloux Y, Gerfaud-Valentin M, Isaac S, et al. Sarcoidosis: a clinical overview from symptoms to diagnosis. Cells. 2021;10:766.
Gupta D, Agarwal R, Aggarwal AN, Jindal SK. Sarcoidosis and tuberculosis: the same disease with different manifestations or similar manifestations of different disorders. Curr Opin Pulm Med. 2012;18:506–16.
pubmed: 22759770 doi: 10.1097/MCP.0b013e3283560809
Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol. 2011;45:899–905.
pubmed: 21659662 pmcid: 3361363 doi: 10.1165/rcmb.2010-0433TR
Orme IM, Basaraba RJ. The formation of the granuloma in tuberculosis infection. Semin Immunol. 2014;26:601–9.
pubmed: 25453231 doi: 10.1016/j.smim.2014.09.009
Binesh F, Halvani H, Navabii H. Systemic sarcoidosis with caseating granuloma. BMJ Case Rep. 2012;2012:bcr0520114278.
Nair PN. On the causes of persistent apical periodontitis: a review. Int Endod J. 2006;39:249–81.
pubmed: 16584489 doi: 10.1111/j.1365-2591.2006.01099.x
Menon N, Kishen A. Nociceptor-macrophage interactions in apical periodontitis: how biomolecules link inflammation with pain. Biomolecules. 2023;13:1193.
Marton IJ, Kiss C. Protective and destructive immune reactions in apical periodontitis. Oral Microbiol Immunol. 2000;15:139–50.
pubmed: 11154396 doi: 10.1034/j.1399-302x.2000.150301.x
Shen J, Zhang H, Jin S, Li N, Fan J. [One year evaluation of endodontic microsurgery in 54 cases with persistent apical periodontitis]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2012;30:388–92.
pubmed: 22934495
Budvytiene I, Banaei N. Simple processing of formalin-fixed paraffin-embedded tissue for accurate testing with the Xpert MTB/RIF assay. J Clin Microbiol. 2020;58:10–1128.
Knopf J, Sjowall J, Frodlund M, Hinkula J, Herrmann M, Sjowall C. NET formation in systemic lupus erythematosus: changes during the COVID-19 pandemic. Cells. 2022;11:2619.
Niazi MK, Beamer G, Gurcan MN. Detecting and characterizing cellular responses to Mycobacterium tuberculosis from histology slides. Cytom A. 2014;85:151–61.
doi: 10.1002/cyto.a.22424
Njau AN, Gakinya SM, Sayed S, Moloo Z. Xpert((R)) MTB/RIF assay on formalin-fixed paraffin-embedded tissues in the diagnosis of extrapulmonary tuberculosis. Afr J Lab Med. 2019;8:748.
pubmed: 31616616 pmcid: 6779992 doi: 10.4102/ajlm.v8i1.748
Ha H, Kim KH, Park JH, Lee JK, Heo EY, Kim JS, et al. Thromboembolism in Mycobacterium tuberculosis infection: analysis and literature review. Infect Chemother. 2019;51:142–9.
pubmed: 31270993 pmcid: 6609750 doi: 10.3947/ic.2019.51.2.142
Singh J, Herrmann I, Mahajan A, Schauer C, Shan X, Hartmann A, et al. A pleomorphic puzzle: heterogeneous pulmonary vascular occlusions in patients with COVID-19. Int J Mol Sci. 2022;23:15126.
Leppkes M, Knopf J, Naschberger E, Lindemann A, Singh J, Herrmann I, et al. Vascular occlusion by neutrophil extracellular traps in COVID-19. EBioMedicine. 2020;58:102925.
pubmed: 32745993 pmcid: 7397705 doi: 10.1016/j.ebiom.2020.102925
Li Q, Wang Y, Sun Q, Knopf J, Herrmann M, Lin L, et al. Immune response in COVID-19: what is next? Cell Death Differ. 2022;29:1107–22.
pubmed: 35581387 pmcid: 9110941 doi: 10.1038/s41418-022-01015-x
Rahlwes KC, Dias BRS, Campos PC, Alvarez-Arguedas S, Shiloh MU. Pathogenicity and virulence of Mycobacterium tuberculosis. Virulence. 2023;14:2150449.
pubmed: 36419223 pmcid: 9817126 doi: 10.1080/21505594.2022.2150449
Moideen K, Kumar NP, Nair D, Banurekha VV, Bethunaickan R, Babu S. Heightened systemic levels of neutrophil and eosinophil granular proteins in pulmonary tuberculosis and reversal following treatment. Infect Immun. 2018;86:10–1128.
Schechter MC, Buac K, Adekambi T, Cagle S, Celli J, Ray SM, et al. Neutrophil extracellular trap (NET) levels in human plasma are associated with active TB. PLoS ONE. 2017;12:e0182587.
pubmed: 28777804 pmcid: 5544211 doi: 10.1371/journal.pone.0182587
Moreira-Teixeira L, Stimpson PJ, Stavropoulos E, Hadebe S, Chakravarty P, Ioannou M, et al. Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis. Nat Commun. 2020;11:5566.
pubmed: 33149141 pmcid: 7643080 doi: 10.1038/s41467-020-19412-6
Masuda S, Nonokawa M, Futamata E, Nishibata Y, Iwasaki S, Tsuji T, et al. Formation and disordered degradation of neutrophil extracellular traps in necrotizing lesions of anti-neutrophil cytoplasmic antibody-associated vasculitis. Am J Pathol. 2019;189:839–46.
pubmed: 30677396 doi: 10.1016/j.ajpath.2019.01.007
Ramakrishnan L. Revisiting the role of the granuloma in tuberculosis. Nat Rev Immunol. 2012;12:352–66.
pubmed: 22517424 doi: 10.1038/nri3211
Bezanilla M, Drake B, Nudler E, Kashlev M, Hansma PK, Hansma HG. Motion and enzymatic degradation of DNA in the atomic force microscope. Biophys J. 1994;67:2454–9.
pubmed: 7696484 pmcid: 1225630 doi: 10.1016/S0006-3495(94)80733-7
Ravichandran S, Subramani VK, Kim KK. Z-DNA in the genome: from structure to disease. Biophys Rev. 2019;11:383–7.
pubmed: 31119604 pmcid: 6557933 doi: 10.1007/s12551-019-00534-1
Buzzo JR, Devaraj A, Gloag ES, Jurcisek JA, Robledo-Avila F, Kesler T, et al. Z-form extracellular DNA is a structural component of the bacterial biofilm matrix. Cell. 2021;184:5740–58.e17.
pubmed: 34735796 pmcid: 8595767 doi: 10.1016/j.cell.2021.10.010
Herbert A. Z-DNA and Z-RNA in human disease. Commun Biol. 2019;2:7.
pubmed: 30729177 pmcid: 6323056 doi: 10.1038/s42003-018-0237-x
Leshner M, Wang S, Lewis C, Zheng H, Chen XA, Santy L, et al. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures. Front Immunol. 2012;3:307.
pubmed: 23060885 pmcid: 3463874 doi: 10.3389/fimmu.2012.00307
Stollar BD. Antibodies to DNA. CRC. Crit Rev Biochem. 1986;20:1–36.
doi: 10.3109/10409238609115899
Suck D, Oefner C. Structure of DNase I at 2.0 A resolution suggests a mechanism for binding to and cutting DNA. Nature. 1986;321:620–5.
pubmed: 3713845 doi: 10.1038/321620a0
Englert H, Gobel J, Khong D, Omidi M, Wolska N, Konrath S, et al. Targeting NETs using dual-active DNase1 variants. Front Immunol. 2023;14:1181761.
pubmed: 37287977 pmcid: 10242134 doi: 10.3389/fimmu.2023.1181761
Baka Z, Gyorgy B, Geher P, Buzas EI, Falus A, Nagy G. Citrullination under physiological and pathological conditions. Jt Bone Spine. 2012;79:431–6.
doi: 10.1016/j.jbspin.2012.01.008
Yipp BG, Petri B, Salina D, Jenne CN, Scott BN, Zbytnuik LD, et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med. 2012;18:1386–93.
pubmed: 22922410 pmcid: 4529131 doi: 10.1038/nm.2847
Seper A, Hosseinzadeh A, Gorkiewicz G, Lichtenegger S, Roier S, Leitner DR, et al. Vibrio cholerae evades neutrophil extracellular traps by the activity of two extracellular nucleases. PLoS Pathog. 2013;9:e1003614.
pubmed: 24039581 pmcid: 3764145 doi: 10.1371/journal.ppat.1003614
Mawuenyega KG, Forst CV, Dobos KM, Belisle JT, Chen J, Bradbury EM, et al. Mycobacterium tuberculosis functional network analysis by global subcellular protein profiling. Mol Biol Cell. 2005;16:396–404.
pubmed: 15525680 pmcid: 539182 doi: 10.1091/mbc.e04-04-0329
Dang G, Cui Y, Wang L, Li T, Cui Z, Song N, et al. Extracellular sphingomyelinase Rv0888 of Mycobacterium tuberculosis contributes to pathological lung injury of mycobacterium smegmatis in mice via inducing formation of neutrophil extracellular traps. Front Immunol. 2018;9:677.
pubmed: 29670633 pmcid: 5893642 doi: 10.3389/fimmu.2018.00677
Dang G, Cao J, Cui Y, Song N, Chen L, Pang H, et al. Characterization of Rv0888, a novel extracellular nuclease from Mycobacterium tuberculosis. Sci Rep. 2016;6:19033.
pubmed: 26742696 pmcid: 4733049 doi: 10.1038/srep19033
Datta M, Via LE, Kamoun WS, Liu C, Chen W, Seano G, et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc Natl Acad Sci USA. 2015;112:1827–32.
pubmed: 25624495 pmcid: 4330784 doi: 10.1073/pnas.1424563112

Auteurs

Leticija Zlatar (L)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. Leticija.Zlatar@uk-erlangen.de.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. Leticija.Zlatar@uk-erlangen.de.

Jasmin Knopf (J)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.

Jeeshan Singh (J)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Han Wang (H)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Marco Muñoz-Becerra (M)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Irmgard Herrmann (I)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Rebecca C Chukwuanukwu (RC)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Immunology Unit, Medical Laboratory Science Department, Faculty of Health Sciences, Nnamdi Azikiwe University, Awka, Nigeria.

Markus Eckstein (M)

CCC Comprehensive Cancer Center (CCC) Erlangen and Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Philip Eichhorn (P)

CCC Comprehensive Cancer Center (CCC) Erlangen and Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Ralf J Rieker (RJ)

CCC Comprehensive Cancer Center (CCC) Erlangen and Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Elisabeth Naschberger (E)

CCC Comprehensive Cancer Center (CCC) Erlangen and Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
Division of Molecular and Experimental Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander Universtität Erlangen-Nürnberg, Erlangen, Germany.

Andreas Burkovski (A)

Microbiology Division, Department of Biology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Veit Krenn (V)

MVZ-Center for Histology, Cytology and Molecular Diagnostics, Trier, Germany.

Rostyslav Bilyy (R)

Lectinotest R&D, Lviv, Ukraine.

Tetiana Butova (T)

Outpatient Department, Merefa District Hospital, Merefa, Ukraine.

Iryna Liskina (I)

Department of Pathomorphology, State Organization "National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine.

Ihor Kalabukha (I)

Department of Surgical Treatment of Tuberculosis and Non-Specific Lung Diseases, State Organization "National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine.

Oleg Khmel (O)

Department of Surgical Treatment of Tuberculosis and Non-Specific Lung Diseases, State Organization "National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine.

Michael Boettcher (M)

Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.

Georg Schett (G)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Dmytro Butov (D)

Department of Infectious Diseases and Phthisiology, Kharkiv National Medical University, Kharkiv, Ukraine.

Anton Tkachenko (A)

Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, Kharkiv, Ukraine.
BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic.

Martin Herrmann (M)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.

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