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Financial support: This work was funded by the Division of Intramural Research, NIAID, NIH. I (G. R. K.) thank the Indian Council of Medical Research (ICMR) for providing the ICMR Postdoctoral Fellowship (PDF).
Authors’ addresses: Gokul Raj Kathamuthu, Kadar Moideen, and Subash Babu, National Institutes of Health, National Institute for Research in Tuberculosis, International Center for Excellence in Research (NIH-NIRT-ICER), Chennai, India, E-mails: gokul.r@nirt.res.in, kadar.m@nirt.res.in, and sbabu@niaid.nih.gov. Rathinam Sridhar, Government Stanley Medical Hospital, Government Hospital of Thoracic Medicine, Chennai, India, E-mail: srihema.1964@gmail.com. Dhanaraj Baskaran, National Institute for Research in Tuberculosis, Chennai, India, E-mail: baskar.d@nirt.res.in.
Note: Supplemental figures appear at www.ajtmh.org.
Abstract.
Lymph node tuberculosis (LNTB) is characterized by the enhanced baseline and antigen-specific production of type 1/17 cytokines and reduced baseline and antigen-specific production of interleukin (IL)-1β and IL-18 at the site of infection when compared with peripheral blood. However, the cytokine profile in the lymph nodes (LNs) of Mycobacterium tuberculosis culture–positive LNTB (LNTB+) and negative LNTB (LNTB−) has not been examined. To address this, we have examined the baseline and mycobacterial antigen–stimulated cytokine levels of type 1 (interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], IL-2), type 2 (IL-4, IL-5, and IL-13), type 17 (IL-17A, IL-17F, and IL-22), pro-inflammatory (IL-1α, IL-1β, IL-18, and granulocyte macrophage colony-stimulating factor [GM-CSF]), and regulatory cytokines (IL-10, transforming growth factor beta [TGF-β]) cytokines in the LN culture supernatants of LNTB+ and LNTB− individuals. We have observed significantly enhanced baseline levels of IL-13 and IL-10 and significantly reduced baseline levels of IL-4 and GM-CSF in LNTB+ individuals compared with LNTB− individuals. By contrast, we have observed significantly enhanced levels of type 1 (IFNγ, TNFα, and IL-2), type 17 (IL-17F and IL-22), and pro-inflammatory (IL-1α and GM-CSF) cytokines and significantly reduced levels of TGFβ in response to purified protein derivative, early secreted antigen-6, and culture filtrate protein-10 antigens in LNTB+ compared with LNTB− individuals. On phorbol 12-myristate 13-acetate/ionomycin stimulation, no significant difference was observed for any of the cytokines examined. Thus, our study revealed several interesting differences in the cytokine profiles of mycobacterial antigen–stimulated LN cultures in LNTB+ and LNTB− individuals. Therefore, we suggest the presence of mycobacteria plays a significant role in driving the cytokine response at the site of infection in LNTB.