Intracellular growth of Mycobacterium avium subspecies and global transcriptional responses in human macrophages after infection

Agdestein, Angelika; Jones, Anya C.; Johansen, Tone Kristin Bjordal; Heffernan, Inger Austrheim; Djønne, Berit; Bosco, Anthony; Olsen, Ingrid

doi:10.1186/1471-2164-15-58

Cited by 13 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on statistical analyses, we conclude that M. avium strains cause significantly more cell injuries and apoptosis. This observation is in accordance with a previous study by Agdestein et al, who characterized the gene expression pattern triggered by two strains of M. avium in human primary macrophages [ 52 ]. As a result, they demonstrated the induction of pro-apoptotic genes, such as RIPK2, BID, and tBID after infection [ 52 ].…”

Section: Discussionsupporting

confidence: 93%

“…This observation is in accordance with a previous study by Agdestein et al, who characterized the gene expression pattern triggered by two strains of M. avium in human primary macrophages [ 52 ]. As a result, they demonstrated the induction of pro-apoptotic genes, such as RIPK2, BID, and tBID after infection [ 52 ]. Likewise, the correlation between apoptosis and virulence of mycobacterial strains is debated [ 53 ].…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

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

et al. 2016

View full text Add to dashboard Cite

BackgroundMycobacterial 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).MethodsHuman lung tissues from 65 donors with a size of 0.5–1 cm3 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.ResultsMorphologic 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.ConclusionWe 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.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

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

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The isolated MAA strain here was proven to have strong virulence (Figure 3 ). Compared to intracellular bacterial replication or macrophage infection ( 59 , 63 ), it was more intuitive to use mortality as an indicator of virulence, especially for a bacterial pathogen of strong virulence.…”

Section: Discussionmentioning

confidence: 99%

Isolation, Identification, and Characterization of a New Highly Pathogenic Field Isolate of Mycobacterium avium spp. avium

Zhu

Peng

et al. 2018

Front. Vet. Sci.

View full text Add to dashboard Cite

Avian tuberculosis is a chronic, contagious zoonotic disease affecting birds, mammals, and humans. The disease is most often caused by Mycobacterium avium spp. avium (MAA). Strain resources are important for research on avian tuberculosis and vaccine development. However, there has been little reported about the newly identified MAA strain in recent years in China. In this study, a new strain was isolated from a fowl with symptoms of avian tuberculosis by bacterial culture. The isolated strain was identified to be MAA by culture, staining, and biochemical and genetic analysis, except for different colony morphology. The isolated strain was Ziehl-Zeelsen staining positive, resistant to p-nitrobenzoic acid, and negative for niacin production, Tween-80 hydrolysis, heat stable catalase and nitrate production. The strain had the DnaJ gene, IS1245, and IS901, as well. Serum agglutination indicated that the MAA strain was of serotype 1. The MAA strain showed strong virulence via mortality in rabbits and chickens. The prepared tuberculin of the MAA strain had similar potency compared to the MAA reference strain and standard tuberculin via a tuberculin skin test. Our studies suggested that this MAA strain tends to be a novel subtype, which might enrich the strain resource of avian tuberculosis.

show abstract

“…Recently, transcriptome analyses such as RNA sequencing (RNA-seq) and microarray have enabled detailed investigations of host responses to NTM infection (8)(9)(10). In these studies, human macrophages were infected with NTM bacteria before transcriptome analyses were performed.…”

Section: Clinical Relevancementioning

confidence: 99%

Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria

Matsuyama¹,

Martins²,

Shallom

et al. 2018

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

The incidence of pulmonary nontuberculous mycobacteria (NTM) disease is increasing, but host responses in respiratory epithelium infected with NTM are not fully understood. In this work, we aimed to identify infection-relevant gene expression signatures of NTM infection of the respiratory epithelium. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium subsp. avium (MAC) or Mycobacterium abscessus subsp. abscessus (MAB). We used cells from four different donors to obtain generalizable data. Differentiated respiratory epithelial cells at the ALI were infected with MAC or MAB at a multiplicity of infection of 100:1 or 1,000:1, and RNA sequencing was performed at Days 1 and 3 after infection. In response to infection, we found down-regulation of ciliary genes but upregulation of genes associated with cytokines/chemokines, such as IL-32, and cholesterol biosynthesis. Inflammatory response genes tended to be more upregulated by MAB than by MAC infection. Primary respiratory epithelial cell infection with NTM at the ALI identified ciliary function, cholesterol biosynthesis, and cytokine/chemokine production as major host responses to infection. Some of these pathways may be amenable to therapeutic manipulation.

show abstract

Intracellular growth of Mycobacterium avium subspecies and global transcriptional responses in human macrophages after infection

Cited by 13 publications

References 41 publications

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

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

Isolation, Identification, and Characterization of a New Highly Pathogenic Field Isolate of Mycobacterium avium spp. avium

Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria

Contact Info

Product

Resources

About