A balanced microbiota of the gastrointestinal tract (GIT) is a prerequisite for a healthy host. The GIT microbiota in preterm infants is determined by the method of delivery and nutrition. Probiotics can improve the GIT microbiota balance and suitable animal models are required to verify their harmlessness. Preterm gnotobiotic piglets were colonized with Lactobacillus rhamnosus GG (LGG) to evaluate its safety and possible protective action against infection with an enteric pathogen, Salmonella Typhimurium (ST). Clinical signs (anorexia, somnolence, fever and diarrhea), bacterial interference and translocation, intestinal histopathology, transcriptions of claudin-1, occludin and interferon (IFN)-γ, intestinal and systemic protein levels of interleukin (IL)-8, IL-12/23 p40 and IFN-γ were compared among (i) germ-free, (ii) LGG-colonized, (iii) ST-infected and (iv) LGG-colonized and subsequently ST-infected piglets for 24 h. Both LGG and ST-colonized the GIT; LGG translocated in some cases into mesenteric lymph nodes and the spleen but did not cause bacteremia and clinical changes. ST caused clinical signs of gastroenteritis, translocated into mesenteric lymph nodes, the spleen, liver and blood, increased claudin-1 and IFN-γ transcriptions, but decreased occludin transcription and increased local and systemic levels of IL-8 and IL-12/23 p40. Previous colonization with LGG reduced ST colonization in the jejunum and translocation into the liver, spleen and blood. It partially ameliorated histopathological changes in the intestine, reduced IL-8 levels in the jejunum and plasma and IL-12/23 p40 in the jejunum. The preterm gnotobiotic piglet model of the vulnerable preterm immunocompromised infant is useful to verify the safety of probiotics and evaluate their protective effect.
- MeSH
- bakteriální translokace MeSH
- cytokiny analýza MeSH
- gnotobiologické modely MeSH
- Lacticaseibacillus rhamnosus * MeSH
- prasata MeSH
- předčasný porod mikrobiologie MeSH
- probiotika farmakologie MeSH
- proteiny těsného spoje genetika MeSH
- Salmonella typhimurium růst a vývoj MeSH
- střeva mikrobiologie patologie MeSH
- střevní mikroflóra MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4+ T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD.
- MeSH
- aktivace lymfocytů MeSH
- buňky Th17 imunologie metabolismus MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- exprese genu MeSH
- kůže imunologie metabolismus MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- pohyb buněk imunologie MeSH
- proteiny intermediálních filament nedostatek MeSH
- proteiny těsného spoje genetika metabolismus MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- Th1 buňky imunologie metabolismus MeSH
- Th2 buňky imunologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH