Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease
Abstract
:1. Introduction
2. Results
2.1. DC Characterization, Induction of CD80 and CD86 and Cytokine Production
2.2. Expression of TLRs, Integrin ß8 (ITG ß8) and IL-12p40
3. Discussion
4. Materials and Methods
4.1. Sample Collection and Probiotic Strains
4.2. Generation and Stimulation of DCs
4.3. Cytokine Measurement, Quantitative RT-PCR and Statistical Analysis
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Lloyd-Price, J.; Arze, C.; Ananthakrishnan, A.N.; Schirmer, M.; Avila-Pacheco, J.; Poon, T.W.; Andrews, E.; Ajami, N.J.; Bonham, K.S.; Brislawn, C.J.J.N. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 2019, 569, 655–662. [Google Scholar] [CrossRef] [PubMed]
- Sun, Y.; Li, L.; Xia, Y.; Li, W.; Wang, K.; Wang, L.; Miao, Y.; Ma, Z. The gut microbiota heterogeneity and assembly changes associated with the IBD. Sci. Rep. 2019, 9, 440. [Google Scholar] [CrossRef] [PubMed]
- Coskun, M. Intestinal Epithelium in Inflammatory Bowel Disease. Front. Med. 2014, 1, 24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Obregon, C.; Kumar, R.; Pascual, M.A.; Vassalli, G.; Golshayan, D. Update on Dendritic Cell-Induced Immunological and Clinical Tolerance. Front. Immunol. 2017, 8, 1514. [Google Scholar] [CrossRef] [Green Version]
- Audiger, C.; Rahman, M.J.; Yun, T.J.; Tarbell, K.V.; Lesage, S. The Importance of Dendritic Cells in Maintaining Immune Tolerance. J. Immunol. 2017, 198, 2223–2231. [Google Scholar] [CrossRef] [Green Version]
- Phillips, B.E.; Garciafigueroa, Y.; Trucco, M.; Giannoukakis, N. Clinical Tolerogenic Dendritic Cells: Exploring Therapeutic Impact on Human Autoimmune Disease. Front. Immunol. 2017, 8, 1279. [Google Scholar] [CrossRef] [Green Version]
- Flórez-Grau, G.; Zubizarreta, I.; Cabezón, R.; Villoslada, P.; Benítez-Ribas, D. Tolerogenic Dendritic Cells as a Promising Antigen-Specific Therapy in the Treatment of Multiple Sclerosis and Neuromyelitis Optica From Preclinical to Clinical Trials. Front. Immunol. 2018, 9, 1169. [Google Scholar] [CrossRef] [Green Version]
- Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514. [Google Scholar] [CrossRef] [Green Version]
- Saarela, M. Safety aspects of Lactobacillus and Bifidobacterium species originating from human oro-gastrointestinal tract or from probiotic products. Microb. Ecol. Health Dis. 2009, 14, 234–241. [Google Scholar] [CrossRef]
- Azad, A.K.; Sarker, M.; Li, T.; Yin, J. Probiotic Species in the Modulation of Gut Microbiota: An Overview. BioMed Res. Int. 2018, 2018, 9478630. [Google Scholar] [CrossRef] [Green Version]
- Wu, C.; Ouyang, M.; Guo, Q.; Jia, J.; Liu, R.; Jiang, Y.; Wu, M.; Shen, S. Changes in the intestinal microecology induced by bacillus subtilis inhibit the occurrence of ulcerative colitis and associated cancers: A study on the mechanisms. Am. J. Cancer Res. 2019, 9, 872–886. [Google Scholar] [PubMed]
- Elshaghabee, F.M.F.; Rokana, N.; Gulhane, R.D.; Sharma, C.; Panwar, H. Bacillus As Potential Probiotics: Status, Concerns, and Future Perspectives. Front. Microbiol. 2017, 8, 1490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, W.; Shen, J.; Bo, T.; Peng, L.; Xu, H.; Nasser, M.I.; Zhuang, Q.; Zhao, M. Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation. J. Immunol. Res. 2019, 2019, 1603758. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mallon, P.T.; McKay, D.; Kirk, S.J. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst. Rev. 2007. [Google Scholar] [CrossRef]
- Baba, N.; Samson, S.; Bourdet-Sicard, R.; Rubio, M.; Sarfati, M. Commensal bacteria trigger a full dendritic cell maturation program that promotes the expansion of non-Tr1 suppressor T cells. J. Leukoc. Biol. 2008, 84, 468–476. [Google Scholar] [CrossRef] [PubMed]
- Ng, S.C.; Plamondon, S.; Kamm, M.A.; Hart, A.L.; Al-Hassi, H.O.; Guenther, T.; Stagg, A.J.; Knight, S.C. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm. Bowel Dis. 2010, 16, 1286–1298. [Google Scholar] [CrossRef]
- Matsubara, V.H.; Ishikawa, K.H.; Ando-Suguimoto, E.S.; Bueno-Silva, B.; Nakamae, A.E.M.; Mayer, M.P.A. Probiotic Bacteria Alter Pattern-Recognition Receptor Expression and Cytokine Profile in a Human Macrophage Model Challenged with Candida albicans and Lipopolysaccharide. Front. Microbiol. 2017, 8, 2280. [Google Scholar] [CrossRef] [Green Version]
- Zeuthen, L.H.; Fink, L.N.; Frøkiær, H. Toll-like receptor 2 and nucleotide-binding oligomerization domain-2 play divergent roles in the recognition of gut-derived lactobacilli and bifidobacteria in dendritic cells. Immunology 2008, 124, 489–502. [Google Scholar] [CrossRef]
- You, J.; Dong, H.; Mann, E.R.; Knight, S.C.; Yaqoob, P. Probiotic modulation of dendritic cell function is influenced by ageing. Immunobiology 2014, 219, 138–148. [Google Scholar] [CrossRef] [Green Version]
- Manzotti, C.N.; Liu, M.K.P.; Burke, F.; Dussably, L.; Zheng, Y.; Sansom, D. Integration of CD28 and CTLA-4 function results in differential responses of T cells to CD80 and CD86. Eur. J. Immunol. 2006, 36, 1413–1422. [Google Scholar] [CrossRef]
- Wang, T.; Zheng, N.; Luo, Q.; Jiang, L.; He, B.; Yuan, X.; Shen, L. Probiotics Lactobacillus reuteri Abrogates Immune Checkpoint Blockade-Associated Colitis by Inhibiting Group 3 Innate Lymphoid Cells. Front. Immunol. 2019, 10, 1235. [Google Scholar] [CrossRef] [PubMed]
- Luongo, D.; Treppiccione, L.; Sorrentino, A.; Ferrocino, I.; Turroni, S.; Gatti, M.; Di Cagno, R.; Sanz, Y.; Rossi, M. Immune-modulating effects in mouse dendritic cells of lactobacilli and bifidobacteria isolated from individuals following omnivorous, vegetarian and vegan diets. Cytokine 2017, 97, 141–148. [Google Scholar] [CrossRef] [Green Version]
- Dwivedi, M.; Kumar, P.; Laddha, N.C.; Kemp, E.H. Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity. Autoimmun. Rev. 2016, 15, 379–392. [Google Scholar] [CrossRef] [PubMed]
- Christensen, H.R.; Frøkiær, H.; Pestka, J.J.; Frokiaer, H. Lactobacilli Differentially Modulate Expression of Cytokines and Maturation Surface Markers in Murine Dendritic Cells. J. Immunol. 2002, 168, 171–178. [Google Scholar] [CrossRef] [PubMed]
- Amar, Y.; Rizzello, V.; Cavaliere, R.; Campana, S.; De Pasquale, C.; Barberi, C.; Oliveri, D.; Pezzino, G.; Costa, G.; Meddah, A.T.; et al. Divergent signaling pathways regulate IL-12 production induced by different species of Lactobacilli in human dendritic cells. Immunol. Lett. 2015, 166, 6–12. [Google Scholar] [CrossRef] [PubMed]
- Mikulic, J.; Longet, S.; Favre, L.; Benyacoub, J.; Corthesy, B. Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β. Cell. Mol. Immunol. 2016, 14, 546–556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rubtsov, Y.P.; Rudensky, A.Y. TGFbeta signalling in control of T-cell-mediated self-reactivity. Nat Rev Immunol. 2007, 7, 443–453. [Google Scholar] [CrossRef]
- D’Incà, R.; Barollo, M.; Scarpa, M.; Grillo, A.R.; Brun, P.; Vettorato, M.G.; Castagliuolo, I.; Sturniolo, G.C. Rectal Administration of Lactobacillus casei DG Modifies Flora Composition and Toll-Like Receptor Expression in Colonic Mucosa of Patients with Mild Ulcerative Colitis. Dig. Dis. Sci. 2010, 56, 1178–1187. [Google Scholar] [CrossRef]
- Oliva, S.; Di Nardo, G.; Ferrari, F.; Mallardo, S.; Rossi, P.; Patrizi, G.; Cucchiara, S.; Stronati, L. Randomised clinical trial: The effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis. Aliment. Pharmacol. Ther. 2011, 35, 327–334. [Google Scholar] [CrossRef]
- Di Giacinto, C.; Marinaro, M.; Sanchez, M.; Strober, W.; Boirivant, M. Probiotics Ameliorate Recurrent Th1-Mediated Murine Colitis by Inducing IL-10 and IL-10-Dependent TGF-β-Bearing Regulatory Cells. J. Immunol. 2005, 174, 3237–3246. [Google Scholar] [CrossRef] [Green Version]
- Braat, H.; Brande, J.V.D.; Van Tol, E.; Hommes, D.; Peppelenbosch, M.P.; Van Deventer, S. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am. J. Clin. Nutr. 2004, 80, 1618–1625. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Szebeni, B.; Veres, G.; Dezsõfi, A.; Rusai, K.; Vannay, Á.; Mráz, M.; Majorova, E.; Arató, A. Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease. Clin. Exp. Immunol. 2007, 151, 34–41. [Google Scholar] [CrossRef] [PubMed]
- Frolova, L.; Drastich, P.; Rossmann, P.; Klimesova, K.; Tlaskalova-Hogenova, H. Expression of Toll-like Receptor 2 (TLR2), TLR4, and CD14 in Biopsy Samples of Patients With Inflammatory Bowel Diseases: Upregulated Expression of TLR2 in Terminal Ileum of Patients With Ulcerative Colitis. J. Histochem. Cytochem. 2007, 56, 267–274. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dheer, R.; Santaolalla, R.; Davies, J.M.; Lang, J.K.; Phillips, M.C.; Pastorini, C.; Vazquez-Pertejo, M.T.; Abreu, M.T. Intestinal Epithelial Toll-Like Receptor 4 Signaling Affects Epithelial Function and Colonic Microbiota and Promotes a Risk for Transmissible Colitis. Infect. Immun. 2016, 84, 798–810. [Google Scholar] [CrossRef] [Green Version]
- Sanchez-Munoz, F.; Fonseca-Camarillo, G.; A Villeda-Ramírez, M.; Pérez, M.E.M.; Mendivil, E.J.; Barreto-Zuñiga, R.; Uribe, M.; Bojalil, R.; Dominguez-López, A.; Yamamoto-Furusho, J. Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis. BMC Gastroenterol. 2011, 11, 138. [Google Scholar] [CrossRef] [Green Version]
- Bermudez-Brito, M.; Plaza-Diaz, J.; Muñoz-Quezada, S.; Gomez-Llorente, C.; Gil, Á. Probiotic Mechanisms of Action. Ann. Nutr. Metab. 2012, 61, 160–174. [Google Scholar] [CrossRef]
- Hoarau, C.; Lagaraine, C.; Martin, L.; Velge-Roussel, F.; Lebranchu, Y. Supernatant of Bifidobacterium breve induces dendritic cell maturation, activation, and survival through a Toll-like receptor 2 pathway. J. Allergy Clin. Immunol. 2006, 117, 696–702. [Google Scholar] [CrossRef]
- Giahi, L.; Aumueller, E.; Elmadfa, I.; Haslberger, A.G. Regulation of TLR4, p38 MAPkinase, IkappaB and miRNAs by inactivated strains of lactobacilli in human dendritic cells. Benef. Microbes 2012, 3, 91–98. [Google Scholar] [CrossRef]
- Kim, C.H.; Kim, H.G.; Kim, J.Y.; Kim, N.R.; Jung, B.J.; Jeong, J.H.; Chung, D.K. Probiotic genomic DNA reduces the production of pro-inflammatory cytokine tumor necrosis factor-alpha. FEMS Microbiol. Lett. 2012, 328, 13–19. [Google Scholar] [CrossRef] [Green Version]
- Worthington, J.J.; Czajkowska, B.I.; Melton, A.C.; Travis, M.A. Intestinal dendritic cells specialize to activate transforming growth factor-beta and induce Foxp3+ regulatory T cells via integrin alphavbeta8. Gastroenterology 2011, 141, 1802–1812. [Google Scholar] [CrossRef]
- Travis, M.A.; Reizis, B.; Melton, A.C.; Masteller, E.; Tang, Q.; Proctor, J.M.; Wang, Y.; Bernstein, X.; Huang, X.; Reichardt, L.F.; et al. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 2007, 449, 361–365. [Google Scholar] [CrossRef] [PubMed]
- Paidassi, H.; Acharya, M.; Zhang, A.; Mukhopadhyay, S.; Kwon, M.; Chow, C.; Stuart, L.M.; Savill, J.; Lacy-Hulbert, A. Preferential expression of integrin alphavbeta8 promotes generation of regulatory T cells by mouse CD103+ dendritic cells. Gastroenterology 2011, 141, 1813–1820. [Google Scholar] [CrossRef] [Green Version]
- Lacy-Hulbert, A.; Smith, A.M.; Tissire, H.; Barry, M.; Crowley, D.; Bronson, R.T.; Roes, J.; Savill, J.S.; O’Hynes, R. Ulcerative colitis and autoimmunity induced by loss of myeloid v integrins. Proc. Natl. Acad. Sci. USA 2007, 104, 15823–15828. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hart, A.L.; Al-Hassi, H.O.; Rigby, R.J.; Bell, S.J.; Emmanuel, A.V.; Knight, S.C.; Kamm, M.A.; Stagg, A.J. Characteristics of Intestinal Dendritic Cells in Inflammatory Bowel Diseases. Gastroenterology 2005, 129, 50–65. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, M.; Kweon, M.N.; Kuwata, H.; Schreiber, R.D.; Kiyono, H.; Takeda, K.; Akira, S. Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J. Clin. Investig. 2003, 111, 1297–1308. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moschen, A.R.; Tilg, H.; Raine, T. IL-12, IL-23 and IL-17 in IBD: Immunobiology and therapeutic targeting. Nat. Rev. Gastroenterol. Hepatol. 2018, 16, 185–196. [Google Scholar] [CrossRef]
- Benevento, G.; Avellini, C.; Terrosu, G.; Geraci, M.; Lodolo, I.; Sorrentino, D. Diagnosis and assessment of Crohn’s disease: The present and the future. Expert Rev. Gastroenterol. Hepatol. 2010, 4, 757–766. [Google Scholar] [CrossRef]
- Seyedian, S.S.; Nokhostin, F.; Malamir, M.D. A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. J. Med. Life 2019, 12, 113–122. [Google Scholar]
- Bie, Y.; Xu, Q.; Zhang, Z. Isolation of dendritic cells from umbilical cord blood using magnetic activated cell sorting or adherence. Oncol. Lett. 2015, 10, 67–70. [Google Scholar] [CrossRef] [Green Version]
Clinical Features | UC | CD | HC |
---|---|---|---|
Gender | |||
Females | 2 | 2 | |
Males | 3 | 1 | 1 |
Age (years) | 44 ± 2.3 | 42 ± 2.6 | 36 ± 0.57 |
BMI (kg/m2) | 25 ± 2.4 | 19 ± 2.2 | 25 ± 0.86 |
Disease duration (years) | 6.4 ± 4.3 | 7.8 ± 5.2 | - |
Family history | No | No | - |
Intestinal surgery history | No | No | - |
Smoking history | No | No | - |
Phase of diseases | Flare up (Severe) | Flare up (Severe) | |
Medication use | |||
Aminosalicylate | Yes | Yes | - |
Immunomodulators | Yes | Yes | - |
Anti-TNF agents | No | No | - |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ghavami, S.B.; Yadegar, A.; Aghdaei, H.A.; Sorrentino, D.; Farmani, M.; Mir, A.S.; Azimirad, M.; Balaii, H.; Shahrokh, S.; Zali, M.R. Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease. Int. J. Mol. Sci. 2020, 21, 6266. https://doi.org/10.3390/ijms21176266
Ghavami SB, Yadegar A, Aghdaei HA, Sorrentino D, Farmani M, Mir AS, Azimirad M, Balaii H, Shahrokh S, Zali MR. Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease. International Journal of Molecular Sciences. 2020; 21(17):6266. https://doi.org/10.3390/ijms21176266
Chicago/Turabian StyleGhavami, Shaghayegh Baradaran, Abbas Yadegar, Hamid Asadzadeh Aghdaei, Dario Sorrentino, Maryam Farmani, Adil Shamim Mir, Masoumeh Azimirad, Hedieh Balaii, Shabnam Shahrokh, and Mohammad Reza Zali. 2020. "Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease" International Journal of Molecular Sciences 21, no. 17: 6266. https://doi.org/10.3390/ijms21176266