Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses
Conventional T cells exhibit a delayed response to the initial priming of peptide antigens presented by major histocompatibility complex (MHC) proteins. Unlike conventional T cells, mucosal-associated invariant T (MAIT) cells quickly respond to non-peptidic metabolite antigens presented by MHC-relat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01136/full |
| _version_ | 1818180482136801280 |
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| author | Manju Sharma Shuangmin Zhang Liang Niu David M. Lewinsohn Xiang Zhang Xiang Zhang Shouxiong Huang Shouxiong Huang |
| author_facet | Manju Sharma Shuangmin Zhang Liang Niu David M. Lewinsohn Xiang Zhang Xiang Zhang Shouxiong Huang Shouxiong Huang |
| author_sort | Manju Sharma |
| collection | DOAJ |
| description | Conventional T cells exhibit a delayed response to the initial priming of peptide antigens presented by major histocompatibility complex (MHC) proteins. Unlike conventional T cells, mucosal-associated invariant T (MAIT) cells quickly respond to non-peptidic metabolite antigens presented by MHC-related protein 1 (MR1). To elucidate the MR1-dependent activation program of MAIT cells in response to mycobacterial infections, we determined the surface markers, transcriptomic profiles, and effector responses of activated human MAIT cells. Results revealed that mycobacterial-incubated antigen-presenting cells stimulated abundant human CD8+ MAIT cells to upregulate the co-expression of CD69 and CD26, as a combinatorial activation marker. Further transcriptomic analyses demonstrated that CD69+CD26++ CD8+MAIT cells highly expressed numerous genes for mediating anti-mycobacterial immune responses, including pro-inflammatory cytokines, cytolytic molecules, NK cell receptors, and transcription factors, in contrast to inactivated counterparts CD69+/−CD26+/− CD8+MAIT cells. Gene co-expression, enrichment, and pathway analyses yielded high statistical significance to strongly support that activated CD8+ MAIT cells shared gene expression and numerous pathways with NK and CD8+ T cells in activation, cytokine production, cytokine signaling, and effector functions. Flow cytometry detected that activated CD8+MAIT cells produced TNFα, IFNγ, and granulysin to inhibit mycobacterial growth and fight mycobacterial infection. Together, results strongly support that the combinatorial activation marker CD69+CD26++ labels the activated CD8+MAIT cells that develop an innate-like activation program in anti-mycobacterial immune responses. We speculate that the rapid production of anti-mycobacterial effector molecules facilitates MAIT cells to fight early mycobacterial infection in humans. |
| first_indexed | 2024-12-11T21:20:28Z |
| format | Article |
| id | doaj.art-b7c6c07d52f643b29199178ffd055e42 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T21:20:28Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7c6c07d52f643b29199178ffd055e422022-12-22T00:50:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-06-011110.3389/fimmu.2020.01136543964Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial ResponsesManju Sharma0Shuangmin Zhang1Liang Niu2David M. Lewinsohn3Xiang Zhang4Xiang Zhang5Shouxiong Huang6Shouxiong Huang7Division of Environmental Genetics and Molecular Toxicology, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Environmental Genetics and Molecular Toxicology, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Biostatistics and Bioinformatics, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesPulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, United StatesDivision of Environmental Genetics and Molecular Toxicology, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesGenomics, Epigenomics and Sequencing Core, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDivision of Environmental Genetics and Molecular Toxicology, Department of Environmental and Public Health Sciences, University of Cincinnati College of Medicine, Cincinnati, OH, United StatesImmunobiology Graduate Program, Cincinnati Children's Hospital, Cincinnati, OH, United StatesConventional T cells exhibit a delayed response to the initial priming of peptide antigens presented by major histocompatibility complex (MHC) proteins. Unlike conventional T cells, mucosal-associated invariant T (MAIT) cells quickly respond to non-peptidic metabolite antigens presented by MHC-related protein 1 (MR1). To elucidate the MR1-dependent activation program of MAIT cells in response to mycobacterial infections, we determined the surface markers, transcriptomic profiles, and effector responses of activated human MAIT cells. Results revealed that mycobacterial-incubated antigen-presenting cells stimulated abundant human CD8+ MAIT cells to upregulate the co-expression of CD69 and CD26, as a combinatorial activation marker. Further transcriptomic analyses demonstrated that CD69+CD26++ CD8+MAIT cells highly expressed numerous genes for mediating anti-mycobacterial immune responses, including pro-inflammatory cytokines, cytolytic molecules, NK cell receptors, and transcription factors, in contrast to inactivated counterparts CD69+/−CD26+/− CD8+MAIT cells. Gene co-expression, enrichment, and pathway analyses yielded high statistical significance to strongly support that activated CD8+ MAIT cells shared gene expression and numerous pathways with NK and CD8+ T cells in activation, cytokine production, cytokine signaling, and effector functions. Flow cytometry detected that activated CD8+MAIT cells produced TNFα, IFNγ, and granulysin to inhibit mycobacterial growth and fight mycobacterial infection. Together, results strongly support that the combinatorial activation marker CD69+CD26++ labels the activated CD8+MAIT cells that develop an innate-like activation program in anti-mycobacterial immune responses. We speculate that the rapid production of anti-mycobacterial effector molecules facilitates MAIT cells to fight early mycobacterial infection in humans.https://www.frontiersin.org/article/10.3389/fimmu.2020.01136/fullmucosal-associated invariant T (MAIT) cellstranscriptomeMHC-related protein 1 (MR1)Mycobacterium tuberculosisinnate-like activation |
| spellingShingle | Manju Sharma Shuangmin Zhang Liang Niu David M. Lewinsohn Xiang Zhang Xiang Zhang Shouxiong Huang Shouxiong Huang Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses Frontiers in Immunology mucosal-associated invariant T (MAIT) cells transcriptome MHC-related protein 1 (MR1) Mycobacterium tuberculosis innate-like activation |
| title | Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses |
| title_full | Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses |
| title_fullStr | Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses |
| title_full_unstemmed | Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses |
| title_short | Mucosal-Associated Invariant T Cells Develop an Innate-Like Transcriptomic Program in Anti-mycobacterial Responses |
| title_sort | mucosal associated invariant t cells develop an innate like transcriptomic program in anti mycobacterial responses |
| topic | mucosal-associated invariant T (MAIT) cells transcriptome MHC-related protein 1 (MR1) Mycobacterium tuberculosis innate-like activation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01136/full |
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