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.
Highlights
Mycobacterium tuberculosis (Mtb) infects one-third of humans and causes almost 1.3 million deaths per year [1]
Fifty-nine percent of the HHCs were latent tuberculosis infection (LTBI)-positive at baseline, and 2.53% of the HHCs progressed to active TB disease during follow-up
In γ-irradiated Mtb (γ-Mtb)–stimulated PBMCs, we found higher expression of TR1α on NK and T cells compared with unstimulated PBMCs (Figure 5A)
Summary
Mycobacterium tuberculosis (Mtb) infects one-third of humans and causes almost 1.3 million deaths per year [1]. 90% of infected persons have latent tuberculosis infection (LTBI) and remain well, but 10% develop primary tuberculosis (TB) soon after infection or reactivation of TB many years later [2, 3]. Only a small percentage of persons with LTBI develop TB and are required to complete treatment regimens; approximately 13%–42% of individuals prescribed treatment, fail to complete therapy [4, 5]. Severe immunosuppression due to HIV infection and treatment with corticosteroids and anti-TNF blockers markedly increase the risk of the progression of LTBI to active TB [6,7,8,9]. Among persons who are not clinically immunocompromised, limited information is available about other immune mechanisms that favor the progression of LTBI to TB [10,11,12,13,14,15,16,17,18,19,20,21]
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