Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk
Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati
Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati
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Research Article Immunology Pulmonology

Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk

Abstract

In the current study, we followed 839 household contacts (HHCs) of tuberculosis (TB) patients for 2 years and identified the factors that enhanced the development of TB. Fourteen of the 17 HHCs who progressed to TB were in the 15- to 30-year-old age group. At baseline (the “0“ time point, when all the individuals were healthy), the concentration of the thyroid hormone thyroxine (T4) was lower, and there were increased numbers of Tregs in PBMCs of TB progressors. At baseline, PBMCs from TB progressors stimulated with early secretory antigenic target 6 (ESAT-6) and 10 kDa culture filtrate antigen (CFP-10) produced less IL-1α. Thyroid hormones inhibited Mycobacterium tuberculosis (Mtb) growth in macrophages in an IL-1α–dependent manner. Mtb-infected Thra1PV/+ (mutant thyroid hormone receptor) mice had increased mortality and reduced IL-1α production. Our findings suggest that young HHCs who exhibit decreased production of thyroid hormones are at high risk of developing active TB disease.

Authors

Kamakshi Prudhula Devalraju, Deepak Tripathi, Venkata Sanjeev Kumar Neela, Padmaja Paidipally, Rajesh Kumar Radhakrishnan, Karan P. Singh, Mohammad Soheb Ansari, Martin Jaeger, Romana T. Netea-Maier, Mihai G. Netea, Sunmi Park, Sheue-yann Cheng, Vijaya Lakshmi Valluri, Ramakrishna Vankayalapati

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Figure 2

Immune cell distribution in the PBMCs of household contacts of TB patients.

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Immune cell distribution in the PBMCs of household contacts of TB patien...
PBMCs were isolated from age-matched non-TB progressors (n = 87) and TB progressors (n = 12) at baseline and follow-up (when the progressors were registered as having active TB), and the percentages of (A) CD14+, (B) CD14+CD16+, (C) CD16+CD56+, (D) CD3–CD56+, (E) CD3–CD56+CD27+CCR7+, (F) CD3+, (G) CD4+, and (H) CD4+CD25+FoxP3+ cells were determined by flow cytometry. The data from 87 nonprogressors and 12 progressors are shown. All the age-matched, non-TB progressors were healthy, nonsmoking, and nonalcoholic and were without any immunosuppressive conditions at baseline or follow-up. Data from smoking and alcoholic progressors were not included. P values were determined using 1-way ANOVA with Tukey’s multiple-comparison test. The mean ± SEM and P values are shown.