High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity
Natural killer (NK) and invariant NKT (iNKT) cells are unique innate lymphocytes that coordinate diverse immune responses and display antimycobacterial potential. However, the role of NK and iNKT cells expressing cytokines, cytotoxic, and immune markers in latent tuberculosis (LTB), diabetes mellitu...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/2422790 |
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| author | Gokul Raj Kathamuthu Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu |
| author_facet | Gokul Raj Kathamuthu Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu |
| author_sort | Gokul Raj Kathamuthu |
| collection | DOAJ |
| description | Natural killer (NK) and invariant NKT (iNKT) cells are unique innate lymphocytes that coordinate diverse immune responses and display antimycobacterial potential. However, the role of NK and iNKT cells expressing cytokines, cytotoxic, and immune markers in latent tuberculosis (LTB), diabetes mellitus (DM), or preDM (PDM) and nonDM (NDM) comorbidities is not known. Thus, we have studied the unstimulated (UNS), Mycobacterium tuberculosis (Mtb [PPD, WCL]), and mitogen (P/I)-stimulated NK and iNKT cells expressing Type 1 (IFNγ, TNFα, and IL-2), Type 17 (IL-17A, IL-17F, and IL-22) cytokines, cytotoxic (perforin, granzyme B, and granulysin) and immune (GMCSF, PD-1, and CD69) markers in LTB comorbidities by dimensionality reduction and flow cytometry. Our results suggest that LTB DM and PDM individuals express diverse NK and iNKT cell immune clusters compared to LTB NDM individuals. In UNS condition, frequencies of NK and iNKT cells expressing markers are not significantly different. After Mtb antigen stimulation, NK cell expressing [Type 1 (IFNγ, TNFα, and IL-2), GMCSF in PPD and IFNγ in WCL), Type 17 [(IL-17A), PD-1 in PPD), (IL-17A, IL-17F, and IL-22), PD-1 in WCL], and cytotoxic (perforin, granzyme B in PPD, and WCL)] marker frequencies were significantly reduced in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, iNKT cells expressing [Type 1 (IFNγ, IL-2), GMCSF in PPD), TNFα, GMCSF in WCL), Type 17 (IL-17A), PD-1 in PPD, IL-17F in WCL) cytokines were increased and cytotoxic or immune (perforin, granzyme B, granulysin), CD69 in PPD, perforin and CD69 in WCL] marker frequencies were significantly diminished in LTB DM and/or PDM compared to LTB NDM individuals. Finally, NK and iNKT cell frequencies did not exhibit significant differences upon positive control antigen stimulation between the study population. Therefore, altered NK cell and iNKT cells expressing cytokines, cytotoxic, and immune markers are characteristic features in LTB PDM/DM comorbidities. |
| format | Article |
| id | doaj-art-fbd521ff77ac4561b07c4d394b717905 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-fbd521ff77ac4561b07c4d394b7179052025-02-03T01:20:11ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/2422790High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes ComorbidityGokul Raj Kathamuthu0Nathella Pavan Kumar1Kadar Moideen2Pradeep A. Menon3Subash Babu4National Institutes of Health-NIRT-International Center for Excellence in ResearchNational Institutes of Health-NIRT-International Center for Excellence in ResearchNational Institute for Research in Tuberculosis (NIRT)National Institute for Research in Tuberculosis (NIRT)National Institutes of Health-NIRT-International Center for Excellence in ResearchNatural killer (NK) and invariant NKT (iNKT) cells are unique innate lymphocytes that coordinate diverse immune responses and display antimycobacterial potential. However, the role of NK and iNKT cells expressing cytokines, cytotoxic, and immune markers in latent tuberculosis (LTB), diabetes mellitus (DM), or preDM (PDM) and nonDM (NDM) comorbidities is not known. Thus, we have studied the unstimulated (UNS), Mycobacterium tuberculosis (Mtb [PPD, WCL]), and mitogen (P/I)-stimulated NK and iNKT cells expressing Type 1 (IFNγ, TNFα, and IL-2), Type 17 (IL-17A, IL-17F, and IL-22) cytokines, cytotoxic (perforin, granzyme B, and granulysin) and immune (GMCSF, PD-1, and CD69) markers in LTB comorbidities by dimensionality reduction and flow cytometry. Our results suggest that LTB DM and PDM individuals express diverse NK and iNKT cell immune clusters compared to LTB NDM individuals. In UNS condition, frequencies of NK and iNKT cells expressing markers are not significantly different. After Mtb antigen stimulation, NK cell expressing [Type 1 (IFNγ, TNFα, and IL-2), GMCSF in PPD and IFNγ in WCL), Type 17 [(IL-17A), PD-1 in PPD), (IL-17A, IL-17F, and IL-22), PD-1 in WCL], and cytotoxic (perforin, granzyme B in PPD, and WCL)] marker frequencies were significantly reduced in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, iNKT cells expressing [Type 1 (IFNγ, IL-2), GMCSF in PPD), TNFα, GMCSF in WCL), Type 17 (IL-17A), PD-1 in PPD, IL-17F in WCL) cytokines were increased and cytotoxic or immune (perforin, granzyme B, granulysin), CD69 in PPD, perforin and CD69 in WCL] marker frequencies were significantly diminished in LTB DM and/or PDM compared to LTB NDM individuals. Finally, NK and iNKT cell frequencies did not exhibit significant differences upon positive control antigen stimulation between the study population. Therefore, altered NK cell and iNKT cells expressing cytokines, cytotoxic, and immune markers are characteristic features in LTB PDM/DM comorbidities.http://dx.doi.org/10.1155/2022/2422790 |
| spellingShingle | Gokul Raj Kathamuthu Nathella Pavan Kumar Kadar Moideen Pradeep A. Menon Subash Babu High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity Journal of Immunology Research |
| title | High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity |
| title_full | High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity |
| title_fullStr | High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity |
| title_full_unstemmed | High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity |
| title_short | High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity |
| title_sort | high dimensionality reduction and immune phenotyping of natural killer and invariant natural killer cells in latent tuberculosis diabetes comorbidity |
| url | http://dx.doi.org/10.1155/2022/2422790 |
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