MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands
Mucosal-associated invariant T (MAIT) cells constitute a highly conserved subset of effector T cells with innate-like recognition of a wide array of bacteria and fungi in humans. Harnessing the potential of these cells could represent a major advance as a new immunotherapy approach to fight difficul...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.02097/full |
| _version_ | 1818862485807038464 |
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| author | Marion Pavlovic Christelle Gross Chahinaize Chili Thomas Secher Emmanuel Treiner Emmanuel Treiner Emmanuel Treiner |
| author_facet | Marion Pavlovic Christelle Gross Chahinaize Chili Thomas Secher Emmanuel Treiner Emmanuel Treiner Emmanuel Treiner |
| author_sort | Marion Pavlovic |
| collection | DOAJ |
| description | Mucosal-associated invariant T (MAIT) cells constitute a highly conserved subset of effector T cells with innate-like recognition of a wide array of bacteria and fungi in humans. Harnessing the potential of these cells could represent a major advance as a new immunotherapy approach to fight difficult-to-treat bacterial infections. However, despite recent advances in the design of potent agonistic ligands for MAIT cells, it has become increasingly evident that adjuvants are required to elicit potent antimicrobial effector functions by these cells, such as IFNγ production and cytotoxicity. Indeed, TCR triggering alone elicits mostly barrier repair functions in MAIT cells, whereas an inflammatory milieu is required to drive the antibacterial functions. Cytokines such as IL-7, IL-12 and IL-18, IL-15 or more recently type 1 IFN all display an apparently similar ability to synergize with TCR stimulation to induce IFNγ production and/or cytotoxic functions in vitro, but their mechanisms of action are not well established. Herein, we show that MAIT cells feature a build-in mechanism to respond to IFNα. We confirm that IFNα acts directly and specifically on MAIT cells and synergizes with TCR/CD3 triggering to induce maximum cytokine production and cytotoxic functions. We provide evidences suggesting that the preferential activation of the Stat4 pathway is involved in the high sensitivity of MAIT cells to IFNα stimulation. Finally, gene expression data confirm the specific responsiveness of MAIT cells to IFNα and pinpoints specific pathways that could be the target of this cytokine. Altogether, these data highlight the potential of IFNα-inducing adjuvants to maximize MAIT cells responsiveness to purified ligands in order to induce potent anti-infectious responses. |
| first_indexed | 2024-12-19T10:00:37Z |
| format | Article |
| id | doaj.art-d866d73918f846ac991d63638b59a715 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T10:00:37Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d866d73918f846ac991d63638b59a7152022-12-21T20:26:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02097529891MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 LigandsMarion Pavlovic0Christelle Gross1Chahinaize Chili2Thomas Secher3Emmanuel Treiner4Emmanuel Treiner5Emmanuel Treiner6INSERM UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, FranceINSERM UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, FranceINSERM UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, FranceINSERM UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, FranceINSERM UMR 1043, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, FrancePaul Sabatier University Toulouse III, Toulouse, FranceLaboratory of Immunology, Toulouse University Hospital, Toulouse, FranceMucosal-associated invariant T (MAIT) cells constitute a highly conserved subset of effector T cells with innate-like recognition of a wide array of bacteria and fungi in humans. Harnessing the potential of these cells could represent a major advance as a new immunotherapy approach to fight difficult-to-treat bacterial infections. However, despite recent advances in the design of potent agonistic ligands for MAIT cells, it has become increasingly evident that adjuvants are required to elicit potent antimicrobial effector functions by these cells, such as IFNγ production and cytotoxicity. Indeed, TCR triggering alone elicits mostly barrier repair functions in MAIT cells, whereas an inflammatory milieu is required to drive the antibacterial functions. Cytokines such as IL-7, IL-12 and IL-18, IL-15 or more recently type 1 IFN all display an apparently similar ability to synergize with TCR stimulation to induce IFNγ production and/or cytotoxic functions in vitro, but their mechanisms of action are not well established. Herein, we show that MAIT cells feature a build-in mechanism to respond to IFNα. We confirm that IFNα acts directly and specifically on MAIT cells and synergizes with TCR/CD3 triggering to induce maximum cytokine production and cytotoxic functions. We provide evidences suggesting that the preferential activation of the Stat4 pathway is involved in the high sensitivity of MAIT cells to IFNα stimulation. Finally, gene expression data confirm the specific responsiveness of MAIT cells to IFNα and pinpoints specific pathways that could be the target of this cytokine. Altogether, these data highlight the potential of IFNα-inducing adjuvants to maximize MAIT cells responsiveness to purified ligands in order to induce potent anti-infectious responses.https://www.frontiersin.org/article/10.3389/fimmu.2020.02097/fullMAIT cellstype 1 interferonsco-stimulationcytokinesvaccines |
| spellingShingle | Marion Pavlovic Christelle Gross Chahinaize Chili Thomas Secher Emmanuel Treiner Emmanuel Treiner Emmanuel Treiner MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands Frontiers in Immunology MAIT cells type 1 interferons co-stimulation cytokines vaccines |
| title | MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands |
| title_full | MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands |
| title_fullStr | MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands |
| title_full_unstemmed | MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands |
| title_short | MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands |
| title_sort | mait cells display a specific response to type 1 ifn underlying the adjuvant effect of tlr7 8 ligands |
| topic | MAIT cells type 1 interferons co-stimulation cytokines vaccines |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.02097/full |
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