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The challenge of es...
The challenge of establishing immunocompetent human intestinal 3D models
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- Bergonzini, Anna, 1990- (författare)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Teresa Frisan
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- Avila-Cariño, Javier, 1957- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Umeå Centre for Microbial Research (UCMR),Teresa Frisan
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- Lopez Chiloeches, Maria, 1992- (författare)
- Umeå universitet,Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten),Teresa Frisan
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visa fler...
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- Frisan, Teresa, 1967- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Umeå Centre for Microbial Research (UCMR),Teresa Frisan
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(creator_code:org_t)
- Engelska.
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- Expression of typhoid toxin in Salmonella Typhimurium causes DNA damage, activating the DNA damage response (DDR), in absence of an inflammatory response in the colonic mucosa of infected mice. The anti-inflammatory effect is tissue specific and is not observed in the liver, suggesting that the local immune microenvironment modulates the DDR outcome.To assess the role of the immune cells in the DDR outcome induced by the genotoxigenic Salmonella, we have initiated the development of an immunocompetent 3D colonic mucosal model based on a collagen matrix containing colonic fibroblasts and different subtypes of immune cells, overlayed with colonic epithelial cells.Embedding of peripheral blood mononuclear cells in the collagen matrix did not influenced either the tissue integrity or the activation of the DDR, observed exclusively upon infection with the genotoxigenic strain. However, embedding of T cells, monocytes, or non-polarized macrophages altered the pattern of the DDR and the toxin specific effect was lost. Presence of macrophages was further associated with alteration of the epithelial layer integrity. This effect was infection-dependent, but not toxin specific.Our data demonstrated that addition of immune cells to a 3D mucosal model altered the DDR induced by a genotoxigenic bacterium, highlighting the need to develop and optimize immunocompetent in vitro models.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
Nyckelord
- bacterial genotoxin
- bacteria
- DNA damage response
- organotypic model
- immune cells.
- biology
- biologi
- cellforskning
- cell research
- immunologi
- Immunology
Publikations- och innehållstyp
- vet (ämneskategori)
- ovr (ämneskategori)