TY - JOUR AU - Devalraju, Kamakshi Prudhula AU - Tripathi, Deepak AU - Neela, Venkata Sanjeev Kumar AU - Paidipally, Padmaja AU - Radhakrishnan, Rajesh Kumar AU - Singh, Karan P. AU - Ansari, Mohammad Soheb AU - Jaeger, Martin AU - Netea-Maier, Romana T. AU - Netea, Mihai G. AU - Park, Sunmi AU - Cheng, Sheue-yann AU - Valluri, Vijaya Lakshmi AU - Vankayalapati, Ramakrishna T1 - Reduced thyroxine production in young household contacts of tuberculosis patients increases active tuberculosis disease risk PY - 2021/07/08/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.148271 VL - 6 IS - 13 UR - https://doi.org/10.1172/jci.insight.148271 PB - The American Society for Clinical Investigation ER -