Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity
Antigen-specific gamma-delta (γδ) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.756854/full |
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| author | Gokul Raj Kathamuthu Gokul Raj Kathamuthu Nathella Pavan Kumar Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu Subash Babu |
| author_facet | Gokul Raj Kathamuthu Gokul Raj Kathamuthu Nathella Pavan Kumar Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu Subash Babu |
| author_sort | Gokul Raj Kathamuthu |
| collection | DOAJ |
| description | Antigen-specific gamma-delta (γδ) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and positive control antigen-stimulated γδ T cells expressing Th1 (IFNγ, TNFα, IL-2) and Th17 (IL-17A, IL-17F, IL-22) cytokine as well as cytotoxic (perforin [PFN], granzyme [GZE B], granulysin [GNLSN]) and immune (GMCSF, PD-1, CD69) markers in LTB (DM, PDM, NDM) comorbidities by flow cytometry. In the unstimulated (UNS) condition, we did not observe any significant difference in the frequencies of γδ T cells expressing Th1 and Th17 cytokine, cytotoxic, and immune markers. In contrast, upon PPD antigen stimulation, the frequencies of γδ T cells expressing Th1 (IFNγ, TNFα) and Th17 (IL-17F, IL-22) cytokine, cytotoxic (PFN, GZE B, GNLSN), and immune (CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, upon WCL antigen stimulation, the frequencies of γδ T cells expressing Th1 (TNFα) and Th17 (IL-17A, IL-22) cytokine, cytotoxic (PFN), and immune (PD-1, CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Finally, upon P/I stimulation we did not observe any significant difference in the γδ T cell frequencies expressing cytokine, cytotoxic, and immune markers between the study populations. The culture supernatant levels of IFNγ, TNFα, and IL-17A cytokines were significantly increased in LTB DM and PDM after stimulation with Mtb antigens compared to LTB NDM individuals. Therefore, diminished γδ T cells expressing cytokine, cytotoxic, and other immune markers and elevated levels of cytokines in the supernatants is a characteristic feature of LTB PDM/DM co-morbidities. |
| first_indexed | 2024-12-16T09:02:50Z |
| format | Article |
| id | doaj.art-95154bd01ae547a7a06080daf4454a96 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-16T09:02:50Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-95154bd01ae547a7a06080daf4454a962022-12-21T22:37:08ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-10-011110.3389/fcimb.2021.756854756854Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes ComorbidityGokul Raj Kathamuthu0Gokul Raj Kathamuthu1Nathella Pavan Kumar2Nathella Pavan Kumar3Kadar Moideen4Pradeep A. Menon5Subash Babu6Subash Babu7National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, IndiaIndian Council of Medical Research-National Institute for Research in Tuberculosis (ICMR-NIRT), Chennai, IndiaNational Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, IndiaIndian Council of Medical Research-National Institute for Research in Tuberculosis (ICMR-NIRT), Chennai, IndiaNational Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, IndiaIndian Council of Medical Research-National Institute for Research in Tuberculosis (ICMR-NIRT), Chennai, IndiaNational Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, IndiaLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesAntigen-specific gamma-delta (γδ) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and positive control antigen-stimulated γδ T cells expressing Th1 (IFNγ, TNFα, IL-2) and Th17 (IL-17A, IL-17F, IL-22) cytokine as well as cytotoxic (perforin [PFN], granzyme [GZE B], granulysin [GNLSN]) and immune (GMCSF, PD-1, CD69) markers in LTB (DM, PDM, NDM) comorbidities by flow cytometry. In the unstimulated (UNS) condition, we did not observe any significant difference in the frequencies of γδ T cells expressing Th1 and Th17 cytokine, cytotoxic, and immune markers. In contrast, upon PPD antigen stimulation, the frequencies of γδ T cells expressing Th1 (IFNγ, TNFα) and Th17 (IL-17F, IL-22) cytokine, cytotoxic (PFN, GZE B, GNLSN), and immune (CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, upon WCL antigen stimulation, the frequencies of γδ T cells expressing Th1 (TNFα) and Th17 (IL-17A, IL-22) cytokine, cytotoxic (PFN), and immune (PD-1, CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Finally, upon P/I stimulation we did not observe any significant difference in the γδ T cell frequencies expressing cytokine, cytotoxic, and immune markers between the study populations. The culture supernatant levels of IFNγ, TNFα, and IL-17A cytokines were significantly increased in LTB DM and PDM after stimulation with Mtb antigens compared to LTB NDM individuals. Therefore, diminished γδ T cells expressing cytokine, cytotoxic, and other immune markers and elevated levels of cytokines in the supernatants is a characteristic feature of LTB PDM/DM co-morbidities.https://www.frontiersin.org/articles/10.3389/fcimb.2021.756854/fullγδ T cellsTh1/Th17 cytokinescytotoxic and immune markerslatent tuberculosisdiabetes mellituspre-diabetes |
| spellingShingle | Gokul Raj Kathamuthu Gokul Raj Kathamuthu Nathella Pavan Kumar Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu Subash Babu Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity Frontiers in Cellular and Infection Microbiology γδ T cells Th1/Th17 cytokines cytotoxic and immune markers latent tuberculosis diabetes mellitus pre-diabetes |
| title | Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity |
| title_full | Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity |
| title_fullStr | Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity |
| title_full_unstemmed | Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity |
| title_short | Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity |
| title_sort | decreased frequencies of gamma delta t cells expressing th1 th17 cytokine cytotoxic and immune markers in latent tuberculosis diabetes pre diabetes comorbidity |
| topic | γδ T cells Th1/Th17 cytokines cytotoxic and immune markers latent tuberculosis diabetes mellitus pre-diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.756854/full |
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