Cargando…

Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells

BACKGROUND: Mycobacterial infections remain a significant cause of morbidity and mortality worldwide. Due to limitations of the currently available model systems, there are still comparably large gaps in the knowledge about the pathogenesis of these chronic inflammatory diseases in particular with r...

Descripción completa

Detalles Bibliográficos
Autores principales: Ganbat, Dariimaa, Seehase, Sophie, Richter, Elvira, Vollmer, Ekkehard, Reiling, Norbert, Fellenberg, Kurt, Gaede, Karoline I., Kugler, Christian, Goldmann, Torsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724406/
https://www.ncbi.nlm.nih.gov/pubmed/26803467
http://dx.doi.org/10.1186/s12890-016-0185-5
_version_ 1782411555170680832
author Ganbat, Dariimaa
Seehase, Sophie
Richter, Elvira
Vollmer, Ekkehard
Reiling, Norbert
Fellenberg, Kurt
Gaede, Karoline I.
Kugler, Christian
Goldmann, Torsten
author_facet Ganbat, Dariimaa
Seehase, Sophie
Richter, Elvira
Vollmer, Ekkehard
Reiling, Norbert
Fellenberg, Kurt
Gaede, Karoline I.
Kugler, Christian
Goldmann, Torsten
author_sort Ganbat, Dariimaa
collection PubMed
description BACKGROUND: Mycobacterial infections remain a significant cause of morbidity and mortality worldwide. Due to limitations of the currently available model systems, there are still comparably large gaps in the knowledge about the pathogenesis of these chronic inflammatory diseases in particular with regard to the human host. Therefore, we aimed to characterize the initial phase of mycobacterial infections utilizing a human ex vivo lung tissue culture model designated STST (Short-Term Stimulation of Tissues). METHODS: Human lung tissues from 65 donors with a size of 0.5–1 cm(3) were infected each with two strains of three different mycobacterial species (M. tuberculosis, M. avium, and M. abscessus), respectively. In order to preserve both morphology and nucleic acids, the HOPE® fixation technique was used. The infected tissues were analyzed using histo- and molecular-pathological methods. Immunohistochemistry was applied to identify the infected cell types. RESULTS: Morphologic comparisons between ex vivo incubated and non-incubated lung specimens revealed no noticeable differences. Viability of ex vivo stimulated tissues demonstrated by TUNEL-assay was acceptable. Serial sections verified sufficient diffusion of the infectious agents deep into the tissues. Infection was confirmed by Ziel Neelsen-staining and PCR to detect mycobacterial DNA. We observed the infection of different cell types, including macrophages, neutrophils, monocytes, and pneumocytes-II, which were critically dependent on the mycobacterial species used. Furthermore, different forms of nuclear alterations (karyopyknosis, karyorrhexis, karyolysis) resulting in cell death were detected in the infected cells, again with characteristic species-dependent differences. CONCLUSION: We show the application of a human ex vivo tissue culture model for mycobacterial infections. The immediate primary infection of a set of different cell types and the characteristic morphologic changes observed in these infected human tissues significantly adds to the current understanding of the initial phase of human pulmonary tuberculosis. Further studies are ongoing to elucidate the molecular mechanisms involved in the early onset of mycobacterial infections in the human lung.
format Online
Article
Text
id pubmed-4724406
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-47244062016-01-25 Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells Ganbat, Dariimaa Seehase, Sophie Richter, Elvira Vollmer, Ekkehard Reiling, Norbert Fellenberg, Kurt Gaede, Karoline I. Kugler, Christian Goldmann, Torsten BMC Pulm Med Research Article BACKGROUND: Mycobacterial infections remain a significant cause of morbidity and mortality worldwide. Due to limitations of the currently available model systems, there are still comparably large gaps in the knowledge about the pathogenesis of these chronic inflammatory diseases in particular with regard to the human host. Therefore, we aimed to characterize the initial phase of mycobacterial infections utilizing a human ex vivo lung tissue culture model designated STST (Short-Term Stimulation of Tissues). METHODS: Human lung tissues from 65 donors with a size of 0.5–1 cm(3) were infected each with two strains of three different mycobacterial species (M. tuberculosis, M. avium, and M. abscessus), respectively. In order to preserve both morphology and nucleic acids, the HOPE® fixation technique was used. The infected tissues were analyzed using histo- and molecular-pathological methods. Immunohistochemistry was applied to identify the infected cell types. RESULTS: Morphologic comparisons between ex vivo incubated and non-incubated lung specimens revealed no noticeable differences. Viability of ex vivo stimulated tissues demonstrated by TUNEL-assay was acceptable. Serial sections verified sufficient diffusion of the infectious agents deep into the tissues. Infection was confirmed by Ziel Neelsen-staining and PCR to detect mycobacterial DNA. We observed the infection of different cell types, including macrophages, neutrophils, monocytes, and pneumocytes-II, which were critically dependent on the mycobacterial species used. Furthermore, different forms of nuclear alterations (karyopyknosis, karyorrhexis, karyolysis) resulting in cell death were detected in the infected cells, again with characteristic species-dependent differences. CONCLUSION: We show the application of a human ex vivo tissue culture model for mycobacterial infections. The immediate primary infection of a set of different cell types and the characteristic morphologic changes observed in these infected human tissues significantly adds to the current understanding of the initial phase of human pulmonary tuberculosis. Further studies are ongoing to elucidate the molecular mechanisms involved in the early onset of mycobacterial infections in the human lung. BioMed Central 2016-01-23 /pmc/articles/PMC4724406/ /pubmed/26803467 http://dx.doi.org/10.1186/s12890-016-0185-5 Text en © Ganbat et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ganbat, Dariimaa
Seehase, Sophie
Richter, Elvira
Vollmer, Ekkehard
Reiling, Norbert
Fellenberg, Kurt
Gaede, Karoline I.
Kugler, Christian
Goldmann, Torsten
Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title_full Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title_fullStr Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title_full_unstemmed Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title_short Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
title_sort mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724406/
https://www.ncbi.nlm.nih.gov/pubmed/26803467
http://dx.doi.org/10.1186/s12890-016-0185-5
work_keys_str_mv AT ganbatdariimaa mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT seehasesophie mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT richterelvira mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT vollmerekkehard mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT reilingnorbert mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT fellenbergkurt mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT gaedekarolinei mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT kuglerchristian mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells
AT goldmanntorsten mycobacteriainfectdifferentcelltypesinthehumanlungandcausespeciesdependentcellularchangesininfectedcells