Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis
Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific pro-inflammatory polarization a...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-05-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00191/full |
| _version_ | 1828760470341812224 |
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| author | Alessia ePiermattei Giuseppe eMigliara Giuseppe eMigliara Gabriele eDi Sante Gabriele eDi Sante Maria eFoti Soren Bohos Hayrabedyan Angela ePapagna Maria Concetta eGeloso Maddalena eCorbi Mariagrazia eValentini Alessandro eSgambato Giovanni eDelogu Gabriela eConstantin Francesco eRia |
| author_facet | Alessia ePiermattei Giuseppe eMigliara Giuseppe eMigliara Gabriele eDi Sante Gabriele eDi Sante Maria eFoti Soren Bohos Hayrabedyan Angela ePapagna Maria Concetta eGeloso Maddalena eCorbi Mariagrazia eValentini Alessandro eSgambato Giovanni eDelogu Gabriela eConstantin Francesco eRia |
| author_sort | Alessia ePiermattei |
| collection | DOAJ |
| description | Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses. |
| first_indexed | 2024-12-11T01:13:29Z |
| format | Article |
| id | doaj.art-2b11fd434a694f6d912f058bb8722770 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T01:13:29Z |
| publishDate | 2016-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2b11fd434a694f6d912f058bb87227702022-12-22T01:25:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-05-01710.3389/fimmu.2016.00191191621Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitisAlessia ePiermattei0Giuseppe eMigliara1Giuseppe eMigliara2Gabriele eDi Sante3Gabriele eDi Sante4Maria eFoti5Soren Bohos Hayrabedyan6Angela ePapagna7Maria Concetta eGeloso8Maddalena eCorbi9Mariagrazia eValentini10Alessandro eSgambato11Giovanni eDelogu12Gabriela eConstantin13Francesco eRia14Università Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversity La SapienzaUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversity of Milano BicoccaInstitute of Biology and Immunology of Reproduction Bulgarian Academy of SciencesUniversity of Milano BicoccaUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversity of VeronaUniversità Cattolica del Sacro CuoreMycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00191/fullHost-Pathogen InteractionsInflammationFoxp3TLR2EAE/MS |
| spellingShingle | Alessia ePiermattei Giuseppe eMigliara Giuseppe eMigliara Gabriele eDi Sante Gabriele eDi Sante Maria eFoti Soren Bohos Hayrabedyan Angela ePapagna Maria Concetta eGeloso Maddalena eCorbi Mariagrazia eValentini Alessandro eSgambato Giovanni eDelogu Gabriela eConstantin Francesco eRia Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis Frontiers in Immunology Host-Pathogen Interactions Inflammation Foxp3 TLR2 EAE/MS |
| title | Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| title_full | Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| title_fullStr | Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| title_full_unstemmed | Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| title_short | Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| title_sort | toll like receptor 2 mediates in vivo pro and anti inflammatory effects of mycobacterium tuberculosis and modulates autoimmune encephalomyelitis |
| topic | Host-Pathogen Interactions Inflammation Foxp3 TLR2 EAE/MS |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00191/full |
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