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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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Autores principales: Kathamuthu, Gokul Raj, Kumar, Nathella Pavan, Moideen, Kadar, Menon, Pradeep A., Babu, Subash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886750/
https://www.ncbi.nlm.nih.gov/pubmed/35242883
http://dx.doi.org/10.1155/2022/2422790
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author Kathamuthu, Gokul Raj
Kumar, Nathella Pavan
Moideen, Kadar
Menon, Pradeep A.
Babu, Subash
author_facet Kathamuthu, Gokul Raj
Kumar, Nathella Pavan
Moideen, Kadar
Menon, Pradeep A.
Babu, Subash
author_sort Kathamuthu, Gokul Raj
collection PubMed
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.
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spelling pubmed-88867502022-03-02 High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity Kathamuthu, Gokul Raj Kumar, Nathella Pavan Moideen, Kadar Menon, Pradeep A. Babu, Subash J Immunol Res Research Article 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. Hindawi 2022-02-21 /pmc/articles/PMC8886750/ /pubmed/35242883 http://dx.doi.org/10.1155/2022/2422790 Text en Copyright © 2022 Gokul Raj Kathamuthu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kathamuthu, Gokul Raj
Kumar, Nathella Pavan
Moideen, Kadar
Menon, Pradeep A.
Babu, Subash
High Dimensionality Reduction and Immune Phenotyping of Natural Killer and Invariant Natural Killer Cells in Latent Tuberculosis-Diabetes Comorbidity
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886750/
https://www.ncbi.nlm.nih.gov/pubmed/35242883
http://dx.doi.org/10.1155/2022/2422790
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