Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that is illustrated by improvement of intestinal inflammation and antimicrobial activity against several pathogens. In this study, we evaluated the immunomodulatory properties of the L. acidophilus strain BIO5768 at steady state and upon acute inflammation. Supplementation of naïve mice with BIO5768 heightened the transcript level of some IL-17 target genes encoding for protein with microbicidal activity independently of NOD2 signaling. Of these, the BIO5768-induced expression of Angiogenin-4 was blunted in monocolonized mice that are deficient for the receptor of IL-17 (but not for NOD2). Interestingly, priming of bone marrow derived dendritic cells by BIO5768 enhanced their ability to support the secretion of IL-17 by CD4+ T cells. Equally of importance, the production of IL-22 by type 3 innate lymphoid cells is concomitantly heightened in response to BIO5768. When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was able to alleviate at least partially intestinal inflammation induced by Citrobacter rodentium infection. Furthermore, BIO5768 was also able to improve colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In conclusion, we identify a new potential probiotic strain for the management of inflammatory bowel diseases, and provide some insights into its IL-17-dependent and independent mode of action.
- MeSH
- Bifidobacterium animalis MeSH
- enterobakteriální infekce terapie MeSH
- idiopatické střevní záněty * terapie MeSH
- interleukin-17 MeSH
- kolitida * chemicky indukované terapie mikrobiologie MeSH
- kyselina trinitrobenzensulfonová škodlivé účinky MeSH
- Lactobacillus acidophilus * MeSH
- lymfocyty MeSH
- myši MeSH
- přirozená imunita * MeSH
- probiotika * farmakologie terapeutické užití MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Crohn's disease is linked to a decreased diversity in gut microbiota composition as a potential consequence of an impaired anti-microbial response and an altered polarization of T helper cells. Here, we evaluated the immunomodulatory properties of two potential probiotic strains, namely a Bifidobacterium animalis spp. lactis Bl 5764 and a Lactobacillus reuteri Lr 5454 strains. Both strains improved colitis triggered by either 2,4,6-trinitrobenzenesulfonic acid (TNBS) or Citrobacter rodentium infection in mice. Training of dendritic cells (DC) with Lr 5454 efficiently triggered IL-22 secretion and regulatory T cells induction in vitro, while IL-17A production by CD4+ T lymphocytes was stronger when cultured with DCs that were primed with Bl 5764. This strain was sufficient for significantly inducing expression of antimicrobial peptides in vivo through the Crohn's disease predisposing gene encoding for the nucleotide-binding oligomerization domain, containing protein 2 (NOD2). In contrast, NOD2 was dispensable for the impact on antimicrobial peptide expression in mice that were monocolonized with Lr 5454. In conclusion, our work highlights a differential mode of action of two potential probiotic strains that protect mice against colitis, providing the rational for a personalized supportive preventive therapy by probiotics for individuals that are genetically predisposed to Crohn's disease.
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- Bifidobacterium animalis * MeSH
- Citrobacter rodentium patogenita MeSH
- dendritické buňky fyziologie MeSH
- enterobakteriální infekce mikrobiologie MeSH
- gnotobiologické modely MeSH
- kolitida chemicky indukované mikrobiologie patologie terapie MeSH
- kyselina trinitrobenzensulfonová toxicita MeSH
- Limosilactobacillus reuteri * MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- probiotika farmakologie MeSH
- proteiny asociované s pankreatitidou genetika MeSH
- regulační T-lymfocyty fyziologie MeSH
- střevní mikroflóra MeSH
- T-lymfocyty pomocné-indukující fyziologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- akridiny farmakologie MeSH
- alergeny imunologie MeSH
- alergie imunologie MeSH
- B-lymfocyty účinky léků imunologie MeSH
- G-kvadruplexy * MeSH
- kultivované buňky MeSH
- myši inbrední BALB C MeSH
- ovalbumin imunologie MeSH
- přesmyk imunoglobulinových tříd * MeSH
- zánět imunologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed.
- MeSH
- Atg5 genetika MeSH
- autofagie MeSH
- citráty aplikace a dávkování farmakologie MeSH
- experimentální nádory dietoterapie farmakoterapie imunologie MeSH
- kalorická restrikce metody MeSH
- lidé MeSH
- methotrexát aplikace a dávkování farmakologie MeSH
- monitorování imunologické MeSH
- mutace MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- protoonkogenní proteiny p21(ras) genetika MeSH
- regulační T-lymfocyty účinky léků MeSH
- spermidin aplikace a dávkování farmakologie MeSH
- transplantace nádorů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
