Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis
Tuberculosis (TB) patients show dysregulated immunity, iron metabolism, and anemia. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, Dmt1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, and transferrin receptor) were monitor...
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Frontiers Media S.A.
2023-01-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985538/full |
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author | Sandeep R. Kaushik Sukanya Sahu Hritusree Guha Sourav Saha Ranjit Das Rukuwe-u Kupa Wetetsho Kapfo Trinayan Deka Rumi Basumatary Asunu Thong Arunabha Dasgupta Bidhan Goswami Amit Kumar Pandey Lahari Saikia Lahari Saikia Vinotsole Khamo Anjan Das Ranjan Kumar Nanda |
author_facet | Sandeep R. Kaushik Sukanya Sahu Hritusree Guha Sourav Saha Ranjit Das Rukuwe-u Kupa Wetetsho Kapfo Trinayan Deka Rumi Basumatary Asunu Thong Arunabha Dasgupta Bidhan Goswami Amit Kumar Pandey Lahari Saikia Lahari Saikia Vinotsole Khamo Anjan Das Ranjan Kumar Nanda |
author_sort | Sandeep R. Kaushik |
collection | DOAJ |
description | Tuberculosis (TB) patients show dysregulated immunity, iron metabolism, and anemia. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, Dmt1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, and transferrin receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n = 72, male: 100%, mean age, 42.94 years; range, 17–83 years). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built, which clustered ATB patients away from NTB and healthy controls. Based on the PLS-DA variable importance in projection (VIP) score and analysis of variance (ANOVA), 13 variables were selected as important biosignatures [IL-18, IL-10, IL-13, IFN-γ, TNF-α, IL-5, IL-12 (p70), IL-1β, copper, zinc, selenium, iron, and aluminum]. Interestingly, low iron and selenium levels and high copper and aluminum levels were observed in ATB subjects. Low circulatory levels of transferrin, ferroportin, and hemojuvelin with higher ferritin and ceruloplasmin levels observed in ATB subjects demonstrate an altered iron metabolism, which partially resolved upon 6 months of anti-TB therapy. The identified biosignature in TB patients demonstrated perturbed iron homeostasis with anemia of inflammation, which could be useful targets for the development of host-directed adjunct therapeutics. |
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language | English |
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spelling | doaj.art-9ed2da43056543ba8ddde6aa7a2691052023-01-12T06:16:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.985538985538Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosisSandeep R. Kaushik0Sukanya Sahu1Hritusree Guha2Sourav Saha3Ranjit Das4Rukuwe-u Kupa5Wetetsho Kapfo6Trinayan Deka7Rumi Basumatary8Asunu Thong9Arunabha Dasgupta10Bidhan Goswami11Amit Kumar Pandey12Lahari Saikia13Lahari Saikia14Vinotsole Khamo15Anjan Das16Ranjan Kumar Nanda17Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTranslational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaDepartment of Respiratory Medicine, Agartala Government Medical College, Agartala, Tripura, IndiaDepartment of Respiratory Medicine, Agartala Government Medical College, Agartala, Tripura, IndiaDepartment of Respiratory Medicine, Agartala Government Medical College, Agartala, Tripura, IndiaHealthcare Laboratory and Research Centre, Naga Hospital Authority, Kohima, Nagaland, IndiaHealthcare Laboratory and Research Centre, Naga Hospital Authority, Kohima, Nagaland, IndiaDepartment of Microbiology, Assam Medical College, Dibrugarh, Assam, IndiaDepartment of Microbiology, Assam Medical College, Dibrugarh, Assam, IndiaDistrict Tuberculosis Centre, Kohima, Nagaland, IndiaDepartment of Medicine, Agartala Government Medical College, Agartala, Tripura, IndiaDepartment of Microbiology, Agartala Government Medical College, Agartala, Tripura, IndiaMycobacterial Pathogenesis Laboratory, Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, IndiaDepartment of Microbiology, Assam Medical College, Dibrugarh, Assam, IndiaDepartment of Microbiology, Gauhati Medical College, Guwahati, Assam, IndiaHealthcare Laboratory and Research Centre, Naga Hospital Authority, Kohima, Nagaland, IndiaDepartment of Respiratory Medicine, Agartala Government Medical College, Agartala, Tripura, IndiaTranslational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, IndiaTuberculosis (TB) patients show dysregulated immunity, iron metabolism, and anemia. In this study, circulatory cytokines, trace metals, and iron-related proteins (hepcidin, ferroportin, transferrin, Dmt1, Nramp1, ferritin, ceruloplasmin, hemojuvelin, aconitase, and transferrin receptor) were monitored in case (active tuberculosis patients: ATB) and control (non-tuberculosis: NTB and healthy) study populations (n = 72, male: 100%, mean age, 42.94 years; range, 17–83 years). Using serum elemental and cytokine levels, a partial least square discriminate analysis model (PLS-DA) was built, which clustered ATB patients away from NTB and healthy controls. Based on the PLS-DA variable importance in projection (VIP) score and analysis of variance (ANOVA), 13 variables were selected as important biosignatures [IL-18, IL-10, IL-13, IFN-γ, TNF-α, IL-5, IL-12 (p70), IL-1β, copper, zinc, selenium, iron, and aluminum]. Interestingly, low iron and selenium levels and high copper and aluminum levels were observed in ATB subjects. Low circulatory levels of transferrin, ferroportin, and hemojuvelin with higher ferritin and ceruloplasmin levels observed in ATB subjects demonstrate an altered iron metabolism, which partially resolved upon 6 months of anti-TB therapy. The identified biosignature in TB patients demonstrated perturbed iron homeostasis with anemia of inflammation, which could be useful targets for the development of host-directed adjunct therapeutics.https://www.frontiersin.org/articles/10.3389/fimmu.2022.985538/fulliron metabolismtuberculosisanemia of inflammatiomcytokinesselenium |
spellingShingle | Sandeep R. Kaushik Sukanya Sahu Hritusree Guha Sourav Saha Ranjit Das Rukuwe-u Kupa Wetetsho Kapfo Trinayan Deka Rumi Basumatary Asunu Thong Arunabha Dasgupta Bidhan Goswami Amit Kumar Pandey Lahari Saikia Lahari Saikia Vinotsole Khamo Anjan Das Ranjan Kumar Nanda Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis Frontiers in Immunology iron metabolism tuberculosis anemia of inflammatiom cytokines selenium |
title | Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis |
title_full | Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis |
title_fullStr | Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis |
title_full_unstemmed | Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis |
title_short | Low circulatory Fe and Se levels with a higher IL-6/IL-10 ratio provide nutritional immunity in tuberculosis |
title_sort | low circulatory fe and se levels with a higher il 6 il 10 ratio provide nutritional immunity in tuberculosis |
topic | iron metabolism tuberculosis anemia of inflammatiom cytokines selenium |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.985538/full |
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