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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Main Authors: 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, Vinotsole Khamo, Anjan Das, Ranjan Kumar Nanda
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
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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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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