{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T22:38:22Z","timestamp":1782167902062,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,17]],"date-time":"2020-04-17T00:00:00Z","timestamp":1587081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01 KI 0720"],"award-info":[{"award-number":["01 KI 0720"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01 KI 0720"],"award-info":[{"award-number":["01 KI 0720"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pneumonia is a cause of high morbidity and mortality in humans. Animal models are indispensable to investigate the complex cellular interactions during lung injury and repair in vivo. The time sequence of lesion development and regeneration is described after endobronchial inoculation of calves with Chlamydia psittaci. Calves were necropsied 2\u201337 days after inoculation (dpi). Lesions and presence of Chlamydia psittaci were investigated using histology and immunohistochemistry. Calves developed bronchopneumonia at the sites of inoculation. Initially, Chlamydia psittaci replicated in type 1 alveolar epithelial cells followed by an influx of neutrophils, vascular leakage, fibrinous exudation, thrombosis and lobular pulmonary necrosis. Lesions were most extensive at 4 dpi. Beginning at 7 dpi, the number of chlamydial inclusions declined and proliferation of cuboidal alveolar epithelial cells and sprouting of capillaries were seen at the periphery of necrotic tissue. At 14 dpi, most of the necrosis had been replaced with alveoli lined with cuboidal epithelial cells resembling type 2 alveolar epithelial cells and mild fibrosis, and hyperplasia of organized lymphoid tissue were observed. At 37 dpi, regeneration of pulmonary tissue was nearly complete and only small foci of remodeling remained. The well-defined time course of development and regeneration of necrotizing pneumonia allows correlation of morphological findings with clinical data or treatment regimen.<\/jats:p>","DOI":"10.3390\/ijms21082817","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T04:49:38Z","timestamp":1587444578000},"page":"2817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regeneration of Pulmonary Tissue in a Calf Model of Fibrinonecrotic Bronchopneumonia Induced by Experimental Infection with Chlamydia psittaci"],"prefix":"10.3390","volume":"21","author":[{"given":"Elisabeth M.","family":"Liebler-Tenorio","sequence":"first","affiliation":[{"name":"Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Lambertz","sequence":"additional","affiliation":[{"name":"Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany"},{"name":"Chemisches und Veterin\u00e4runtersuchungsamt Rhein-Ruhr-Wupper (CVUA-RRW), Deutscher Ring 100, 47798 Krefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Ostermann","sequence":"additional","affiliation":[{"name":"Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Sachse","sequence":"additional","affiliation":[{"name":"Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany"},{"name":"Institute of Bioinformatics, Friedrich-Schiller-Universit\u00e4t Jena, Leutragraben 1, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Institute for Molecular Pathogenesis, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburgerstr. 96a, 07743 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12931-018-0781-4","article-title":"Trends in mortality from pneumonia in the Europe union: A temporal analysis of the European detailed mortality database between 2001 and 2014","volume":"19","author":"Marshall","year":"2018","journal-title":"Resp. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/thx.2009.129502","article-title":"Clinical and economic burden of community-acquired pneumonia among adults in Europe","volume":"67","author":"Welte","year":"2012","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1007\/s00134-016-4394-4","article-title":"Community-acquired pneumonia related to intracellular pathogens","volume":"42","author":"Torres","year":"2016","journal-title":"Intensive Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s10096-014-2067-1","article-title":"The aetiology and antibiotic management of community-acquired pneumonia in adults in Europe: A literature review","volume":"33","author":"Torres","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_5","first-page":"876","article-title":"Etiology and treatment of community-acquired pneumonia in ambulatory children","volume":"43","author":"Wubbel","year":"1999","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.3201\/eid2103.140927","article-title":"Mycoplasma pneumoniae and Chlamydia spp. infection in community-acquired pneumonia, Germany, 2011\u20132012","volume":"21","author":"Dumke","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_7","unstructured":"Spoorenberg, S.M.C., Bos, W.J.W., van Hannen, E.J., Dijkstra, F., Heddema, E.R., van Velzen-Blad, H., Heijligenberg, R., Grutters, J.C., de Jongh, B.M., and Ovidius Study Group (2016). Chlamydia psittaci: A relevant cause of community-acquired pneumonia in two Dutch hospitals. Neth. J. Med., 75\u201381."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1242\/dev.098186","article-title":"Lung development: Orchestrating the generation and regeneration of a complex organ","volume":"141","author":"Herriges","year":"2014","journal-title":"Development"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1513\/AnnalsATS.201408-402MG","article-title":"Conceptual approaches to lung injury and repair","volume":"12","author":"Zemans","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_10","first-page":"103","article-title":"Criteria for development of animal models of diseases of the respiratory system","volume":"101","author":"Slauson","year":"1980","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1702133","DOI":"10.1183\/13993003.02133-2017","article-title":"Optimising experimental research in respiratory diseases: An ERS statement","volume":"51","author":"Bonniaud","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.2527\/jas.2008-1088","article-title":"A commentary on domestic animals as dual-purpose models that benefit agricultural and biomedical research","volume":"86","author":"Ireland","year":"2008","journal-title":"J. Anim. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1097\/MCP.0b013e3283521022","article-title":"Necrotizing pneumonia: A rare complication of pneumonia requiring special consideration","volume":"1","author":"Tsaia","year":"2012","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1097\/MCP.0000000000000571","article-title":"Necrotizing pneumonia (aetiology, clinical features and management)","volume":"25","author":"Krutikov","year":"2019","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hilton, B., Tavare, A.N., and Creer, D. (2017). Necrotising pneumonia caused by non-PVL Staphylococcus aureus with 2-year follow-up. BMJ Case Rep., Published Online First: 28.11.2017, bcr-2017-221779.","DOI":"10.1136\/bcr-2017-221779"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1183\/09031936.00099807","article-title":"Necrotising pneumonia is an increasingly detected complication of pneumonia in children","volume":"31","author":"Sawicki","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1007\/s00134-011-2328-8","article-title":"Necrotizing pneumonia in adults: Multidisciplinary management","volume":"37","author":"Alifano","year":"2011","journal-title":"Intens. Care Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1001\/archinte.159.14.1550","article-title":"Prognosis after community-acquired pneumonia in the elderly: A population-based 12-year follow-up study","volume":"159","author":"Koivula","year":"1999","journal-title":"Arch. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Reinhold, P., Ostermann, C., Liebler-Tenorio, E., Berndt, A., Vogel, A., Lambertz, J., Rothe, M., R\u00fcttger, A., Schubert, E., and Sachse, K. (2012). A bovine model of respiratory Chlamydia psittaci infection: Challenge dose titration. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030125"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.tvjl.2012.10.035","article-title":"Dose-dependent effects of Chlamydia psittaci infection on pulmonary gas exchange, innate immunity and acute-phase reaction in a bovine respiratory model","volume":"196","author":"Ostermann","year":"2013","journal-title":"Vet. J."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ostermann, C., R\u00fcttger, A., Schubert, E., Schr\u00f6dl, W., Sachse, K., and Reinhold, P. (2013). Infection, disease, and transmission dynamics in calves after experimental and natural challenge with a bovine Chlamydia psittaci isolate. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064066"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2049-6958-9-10","article-title":"Evaluation of pulmonary dysfunctions and acid\u2013base imbalances induced by Chlamydia psittaci in a bovine model of respiratory infection","volume":"9","author":"Ostermann","year":"2014","journal-title":"Multidiscip. Respir. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Prohl, A., Lohr, M., Ostermann, C., Liebler-Tenorio, E., Berndt, A., Schroedl, W., Rothe, M., Schubert, E., Sachse, K., and Reinhold, P. (2015). Enrofloxacin and macrolides alone or in combination with rifampicin as antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119736"},{"key":"ref_24","first-page":"1","article-title":"Evaluation of antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection: Tetracycline versus tetracycline plus rifampicin","volume":"73","author":"Prohl","year":"2015","journal-title":"FEMS Pathog. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cvfa.2010.04.001","article-title":"Pathogenesis and pathology of bovine pneumonia","volume":"26","author":"Panciera","year":"2010","journal-title":"Vet. Clin. North. Am. Food Anim. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1172\/JCI45961","article-title":"The three R\u2019s of lung health and disease: Repair, remodeling, and regeneration","volume":"121","author":"Beers","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1128\/IAI.73.4.1939-1946.2005","article-title":"Chlamydial infection induces pathobiotype-specific protein tyrosine phosphorylation in epithelial cells","volume":"73","author":"Virok","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1172\/JCI119136","article-title":"Secretion of proinflammatory cytokines by epithelial cells in response to chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis","volume":"99","author":"Rasmussen","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1086\/317608","article-title":"Infection and activation of airway epithelial cells by Chlamydia pneumoniae","volume":"182","author":"Jahn","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev-physiol-022516-034356","article-title":"Mechanism of organ injury and repair by macrophages","volume":"79","author":"Vanella","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8173983","DOI":"10.1155\/2018\/8173983","article-title":"Neutrophils in tissue trauma of the Skin, bone, and lung: Two sides of the same coin","volume":"2018","author":"Kovtun","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_32","first-page":"H385","article-title":"Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins","volume":"275","author":"Carden","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"G705","DOI":"10.1152\/ajpgi.2001.281.3.G705","article-title":"Neutrophil-mediated epithelial injury during transmigration: Role of elastase","volume":"281","author":"Ginzberg","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_34","first-page":"1191","article-title":"The role of leukocytes in the pathogenesis of fibrin deposition in bovine acute lung injury","volume":"138","author":"Car","year":"1991","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1160\/TH07-11-0666","article-title":"Current view on alveolar coagulation and fibrinolysis in acute inflammatory and chronic interstitial lung diseases","volume":"99","author":"Wygrecka","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/imcb.12235","article-title":"Airway macrophages as the guardians of tissue repair in the lung","volume":"97","author":"Puttur","year":"2019","journal-title":"Immunol. Cell. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-2613.2006.00515.x","article-title":"Inflammation-associated remodelling and fibrosis in the lung - a process and an end point","volume":"88","author":"Wallace","year":"2007","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_38","unstructured":"McGavin, M.D., and Zachary, J.F. (2007). Respiratory System. Pathologic Basis of Veterinary Disease, Mosby Elsevier. [4th ed.]."},{"key":"ref_39","first-page":"9","article-title":"Immune-mediated control of chlamydia infection","volume":"10","author":"Roan","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/0014-4800(75)90059-3","article-title":"Transformation of alveolar type 2 cells to type 1 cells following exposure to NO2","volume":"22","author":"Evans","year":"1975","journal-title":"Exp. Mol. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1016\/j.ajpath.2016.05.023","article-title":"Stem cells in lung injury and repair","volume":"186","author":"Chen","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1242\/dev.143784","article-title":"Plasticity in the lung: Making and breaking cell identity","volume":"144","author":"Tata","year":"2017","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1172\/JCI68782","article-title":"Type 2 alveolar cells are stem cells in adult lung","volume":"123","author":"Barkauskas","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1165\/ajrcmb.23.2.f195","article-title":"Mesenchymal regulation of alveolar repair in pulmonary fibrosis","volume":"23","author":"Fang","year":"2000","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_45","first-page":"314","article-title":"Basal lamina scaffold-anatomy and significance for maintenance of orderly tissue structure","volume":"77","author":"Vracko","year":"1974","journal-title":"Am. J. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6727","DOI":"10.1038\/ncomms7727","article-title":"Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung","volume":"6","author":"Jain","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Castillo, J.A., P\u00e9rez, D.B., Ntokou, A., Seeger, W., Morty, R.E., and Ahlbrecht, K. (2018). Understanding alveolarization to induce lung regeneration. BMC Respir. Res., 19.","DOI":"10.1186\/s12931-018-0837-5"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1161\/ATVBAHA.109.185165","article-title":"Mechanisms of vessel branching: Filopodia on endothelial tip cells lead the way","volume":"29","author":"Segura","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1165\/rcmb.2005-0062TR","article-title":"Pulmonary fibrosis: Searching for model answers","volume":"33","author":"Chua","year":"2005","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1046\/j.1365-2613.2002.00220.x","article-title":"Time course of bleomycin-induced lung fibrosis","volume":"83","author":"Izbicki","year":"2002","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_51","first-page":"555","article-title":"The anatomy and physiology of the bovine respiratory system relating to pulmonary disease","volume":"68","author":"Veit","year":"1978","journal-title":"Cornell Vet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.vetmic.2008.09.041","article-title":"DNA microarray-based genotyping of Chlamydophila psittaci strains from culture and clinical samples","volume":"135","author":"Sachse","year":"2009","journal-title":"Vet. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1128\/IAI.01487-05","article-title":"Transcriptional response patterns of Chlamydophila psittaci in different in vitro models of persistent infection","volume":"74","author":"Goellner","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1128\/jb.59.4.509-522.1950","article-title":"The influence of certain salts, amino acids, sugars, and proteins on the stability of rickettsiae","volume":"59","author":"Bovarick","year":"1950","journal-title":"J. Bacteriol."},{"key":"ref_55","first-page":"e51557","article-title":"The bovine lung in biomedical research: Visually guided bronchoscopy, intrabronchial inoculation and in vivo sampling techniques","volume":"89","author":"Prohl","year":"2014","journal-title":"J. Vis. Exp."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/8\/2817\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:45:02Z","timestamp":1760363102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/8\/2817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,17]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["ijms21082817"],"URL":"https:\/\/doi.org\/10.3390\/ijms21082817","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,17]]}}}