RESEARCH ARTICLE


High Secretion of Interleukin-6 and Increased MINCLE Receptor Expression Upon Exposure to Mycobacterial Cord Factor Analog Trehalose-6, 6-Dibehenate (TDB) in Patients with Takayasu Arteritis



Nikhil Gupta#, Jayakanthan Kabeerdoss#, Hindhumathi Mohan, Ruchika Goel, Debashish Danda*
Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India


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© 2018 Gupta et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


# Joint first authors as equal contributors.* Address correspondence to this author at the Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Pincode – 632004; Tel: +91-416-2282529; Fax: +91-416- 2282035; E-mail: debashisdandacmc@hotmail.com


Abstract

Introduction:

Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls.

Materials and Methods:

Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited. PBMCs were cultured with 5µg/ml, 50µg/ml or without any TDB for 48 hours in RPMI medium inside a 5% Co2 incubator. IL-6, TNF-α and IL-17 were measured in cell culture supernatant, which was separated from the cells at the end of the incubation period. Gene expressions of IL-6, IL-8, TNFα, IFN-γ, MINCLE and BCL-10 were quantified in real time PCR using specific primers and SYBR green chemistry.

Results:

Twenty two TA patients and 21 healthy controls were recruited. Both patients and controls showed response by secreting IL-6 and TNF-α upon stimulation by TDB. Relative induction (TDB stimulated TA sample / unstimulated control) of IL-6 was significantly higher in TA [31.88(0.74-168)] patients as compared to healthy controls [1.931(0.644-8.21); p<0.002], when co-cultured with 50µg/ml TDB. The expression of MINCLE, the TDB receptor was higher in TA samples than healthy controls upon TDB stimulation.

Conclusion:

Stimulation with mycobacterial synthetic analogue led to higher secretion of IL-6 and higher expression of MINCLE in PBMCs of patients with TA as compared to healthy controls.

Keywords: Takayasu Arteritis, Trehalose-6, 6-dibehenate (TDB), MINCLE, Interleukin-6, Mycobacterial cord factor.