Intestinal epithelial cells have the capacity to upregulate MHCII molecules in response to certain epithelial-adhesive microbes, such as segmented filamentous bacteria (SFB). However, the mechanism regulating MHCII expression as well as the impact of epithelial MHCII-mediated antigen presentation on T cell responses targeting those microbes remains elusive. Here, we identify the cellular network that regulates MHCII expression on the intestinal epithelium in response to SFB. Since MHCII on the intestinal epithelium is dispensable for SFB-induced Th17 response, we explored other CD4+ T cell-based responses induced by SFB. We found that SFB drive the conversion of cognate CD4+ T cells to granzyme+ CD8α+ intraepithelial lymphocytes. These cells accumulate in small intestinal intraepithelial space in response to SFB. Yet, their accumulation is abrogated by the ablation of MHCII on the intestinal epithelium. Finally, we show that this mechanism is indispensable for the SFB-driven increase in the turnover of epithelial cells in the ileum. This study identifies a previously uncharacterized immune response to SFB, which is dependent on the epithelial MHCII function.
The currently observed high prevalence of allergic diseases has been associated with changes in microbial exposure in industrialized countries. Defined bacterial components represent a new strategy for modulating the allergic immune response. We show that intranasal administration of exopolysaccharide (EPS) isolated from Lacticaseibacillus (L.) rhamnosus LOCK900 induces TGF-β1, IgA, and regulatory FoxP3+ T-cells in the lungs of naïve mice. Using the ovalbumin mouse model, we demonstrate that intranasal administration of EPS downregulates the development of allergic airway inflammation and the Th2 cytokine response in sensitized individuals. At the same time, EPS treatment of sensitized mice, similar to EPS-induced responses in naïve mice, significantly increased the level of total, OVA-specific, and also bacteria-specific IgA in bronchoalveolar lavage and the number of IgA-producing B-cells in the lung tissue of these mice. Thus, EPS derived from L. rhamnosus LOCK900 can be considered a safe candidate for preventing the development of allergic symptoms in the lungs of sensitized individuals upon exposure to an allergen.
- MeSH
- alergie * MeSH
- bronchoalveolární lavážní tekutina MeSH
- imunoglobulin A MeSH
- Lacticaseibacillus rhamnosus * MeSH
- Lacticaseibacillus MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- ovalbumin MeSH
- plíce MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.
- MeSH
- acetylmuramyl-alanyl-isoglutamin farmakologie terapeutické užití MeSH
- buněčná stěna chemie MeSH
- epitelové buňky mikrobiologie fyziologie MeSH
- gnotobiologické modely MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- inzulin metabolismus MeSH
- Lactobacillaceae * fyziologie MeSH
- myši MeSH
- podvýživa * patofyziologie terapie MeSH
- poruchy růstu patofyziologie terapie MeSH
- růst * účinky léků fyziologie MeSH
- signální adaptorový protein Nod2 * metabolismus MeSH
- střeva * mikrobiologie fyziologie MeSH
- střevní mikroflóra * fyziologie MeSH
- střevní sliznice mikrobiologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
