Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain
The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sust...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.890298/full |
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| author | Francesca Gargano Gisella Guerrera Eleonora Piras Barbara Serafini Monica Di Paola Lisa Rizzetto Maria Chiara Buscarinu Viviana Annibali Claudia Vuotto Marco De Bardi Silvia D’Orso Serena Ruggieri Claudio Gasperini Lorenzo Pavarini Lorenzo Pavarini Giovanni Ristori Giovanni Ristori Mario Picozza Barbara Rosicarelli Clara Ballerini Rosella Mechelli Francesco Vitali Duccio Cavalieri Marco Salvetti Daniela F. Angelini Giovanna Borsellino Carlotta De Filippo Luca Battistini |
| author_facet | Francesca Gargano Gisella Guerrera Eleonora Piras Barbara Serafini Monica Di Paola Lisa Rizzetto Maria Chiara Buscarinu Viviana Annibali Claudia Vuotto Marco De Bardi Silvia D’Orso Serena Ruggieri Claudio Gasperini Lorenzo Pavarini Lorenzo Pavarini Giovanni Ristori Giovanni Ristori Mario Picozza Barbara Rosicarelli Clara Ballerini Rosella Mechelli Francesco Vitali Duccio Cavalieri Marco Salvetti Daniela F. Angelini Giovanna Borsellino Carlotta De Filippo Luca Battistini |
| author_sort | Francesca Gargano |
| collection | DOAJ |
| description | The composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae. We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood–brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases. |
| first_indexed | 2024-04-12T08:04:00Z |
| format | Article |
| id | doaj.art-f7cbdaa66c3d48839d8d7721b91190c1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T08:04:00Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f7cbdaa66c3d48839d8d7721b91190c12022-12-22T03:41:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.890298890298Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brainFrancesca Gargano0Gisella Guerrera1Eleonora Piras2Barbara Serafini3Monica Di Paola4Lisa Rizzetto5Maria Chiara Buscarinu6Viviana Annibali7Claudia Vuotto8Marco De Bardi9Silvia D’Orso10Serena Ruggieri11Claudio Gasperini12Lorenzo Pavarini13Lorenzo Pavarini14Giovanni Ristori15Giovanni Ristori16Mario Picozza17Barbara Rosicarelli18Clara Ballerini19Rosella Mechelli20Francesco Vitali21Duccio Cavalieri22Marco Salvetti23Daniela F. Angelini24Giovanna Borsellino25Carlotta De Filippo26Luca Battistini27Neuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyIstituto Superiore di Sanità, Department of Neuroscience, Rome, ItalyUniversity of Florence, Department of Biology, Florence, ItalyResearch and Innovation Centre – Fondazione Edmund Mach, S. Michele all’Adige (TN), ItalyNeurology and Centre for Experimental Neurological therapies (CENTERS), S. Andrea Hospital, Sapienza University, Rome, ItalyNeurology and Centre for Experimental Neurological therapies (CENTERS), S. Andrea Hospital, Sapienza University, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyDepartment of Neuroscience “Lancisi”, S. Camillo Hospital, Rome, ItalyDepartment of Neuroscience “Lancisi”, S. Camillo Hospital, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyUniversity of Florence, Department of Biology, Florence, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeurology and Centre for Experimental Neurological therapies (CENTERS), S. Andrea Hospital, Sapienza University, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyIstituto Superiore di Sanità, Department of Neuroscience, Rome, ItalyUniversity of Florence, Clinical and Experimental Medicine, Florence, ItalyNeurology and Centre for Experimental Neurological therapies (CENTERS), S. Andrea Hospital, Sapienza University, Rome, ItalyNational Research Council, Institute of Agricultural Biology and Biotechnology, Pisa, ItalyUniversity of Florence, Department of Biology, Florence, ItalyNeurology and Centre for Experimental Neurological therapies (CENTERS), S. Andrea Hospital, Sapienza University, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyNational Research Council, Institute of Agricultural Biology and Biotechnology, Pisa, ItalyNeuroimmunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, ItalyThe composition of the intestinal microbiota plays a critical role in shaping the immune system. Modern lifestyle, the inappropriate use of antibiotics, and exposure to pollution have significantly affected the composition of commensal microorganisms. The intestinal microbiota has been shown to sustain inappropriate autoimmune responses at distant sites in animal models of disease, and may also have a role in immune-mediated central nervous system (CNS) diseases such as multiple sclerosis (MS). We studied the composition of the gut mycobiota in fecal samples from 27 persons with MS (pwMS) and in 18 healthy donors (HD), including 5 pairs of homozygous twins discordant for MS. We found a tendency towards higher fungal abundance and richness in the MS group, and we observed that MS twins showed a higher rate of food-associated strains, such as Saccharomyces cerevisiae. We then found that in pwMS, a distinct population of cells with antibacterial and antifungal activity is expanded during the remitting phase and markedly decreases during clinically and/or radiologically active disease. These cells, named MAIT (mucosal-associated invariant T cells) lymphocytes, were significantly more activated in pwMS compared to HD in response to S. cerevisiae and Candida albicans strains isolated from fecal samples. This activation was also mediated by fungal-induced IL-23 secretion by innate immune cells. Finally, immunofluorescent stainings of MS post-mortem brain tissues from persons with the secondary progressive form of the disease showed that MAIT cells cross the blood–brain barrier (BBB) and produce pro-inflammatory cytokines in the brain. These results were in agreement with the hypothesis that dysbiosis of the gut microbiota might determine the inappropriate response of a subset of pathogenic mucosal T cells and favor the development of systemic inflammatory and autoimmune diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2022.890298/fullmultiple sclerosisdysbiosismycobiomeMAIT cellsneuroinflammation |
| spellingShingle | Francesca Gargano Gisella Guerrera Eleonora Piras Barbara Serafini Monica Di Paola Lisa Rizzetto Maria Chiara Buscarinu Viviana Annibali Claudia Vuotto Marco De Bardi Silvia D’Orso Serena Ruggieri Claudio Gasperini Lorenzo Pavarini Lorenzo Pavarini Giovanni Ristori Giovanni Ristori Mario Picozza Barbara Rosicarelli Clara Ballerini Rosella Mechelli Francesco Vitali Duccio Cavalieri Marco Salvetti Daniela F. Angelini Giovanna Borsellino Carlotta De Filippo Luca Battistini Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain Frontiers in Immunology multiple sclerosis dysbiosis mycobiome MAIT cells neuroinflammation |
| title | Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| title_full | Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| title_fullStr | Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| title_full_unstemmed | Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| title_short | Proinflammatory mucosal-associated invariant CD8+ T cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| title_sort | proinflammatory mucosal associated invariant cd8 t cells react to gut flora yeasts and infiltrate multiple sclerosis brain |
| topic | multiple sclerosis dysbiosis mycobiome MAIT cells neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.890298/full |
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