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Journal article
Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased inflammation in intraocular tuberculosis
Scientific reports, v 8(1), pp 13812-15
14 Sep 2018
PMID: 30218032
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Intraocular tuberculosis (IOTB) is amongst the leading causes of uveitis in tropical countries. Despite reports on involvement of proinflammatory cytokines, studies on innate immune responses in disease pathogenesis are lacking. Reports from animal models and patients with pulmonary tuberculosis indicate that defects in toll like receptor (TLR)2 and TLR9 signalling predispose them to tuberculosis. In this context, we investigated the role of TLR2, TLR4 and TLR9 in generation of CD4+ T effector (Teff) cell responses during IOTB. Firstly, the cells in vitreous fluids showed lower expression of TLR2 and TLR9 in IOTB as compared to non-uveitis and non-TB uveitis groups. Next, peripheral CD4+ Teff cells of subjects with IOTB showed decreased proliferative responses and lower induction of Tregs following TLR2 and TLR9 stimulation. Further, TLR9 ligation resulted in increased IFN-γ and IL-17a but decreased expression of IL-10 and TGF-β. Lastly, lower expression of genes involved in TLR9 signalling after direct TLR9 ligation was observed in IOTB. Collectively, our results show that a subdued response to direct TLR2 and TLR9 stimulation in CD4+ T cells is associated with increased proinflammatory responses in IOTB. These findings reveal an important link between innate immune signalling and ensuing adaptive immune responses in IOTB with implications in other forms of extrapulmonary tuberculosis.
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Details
- Title
- Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased inflammation in intraocular tuberculosis
- Creators
- Ravi Kumar Sharma - Post Graduate Institute of Medical Education and ResearchJyoti Sharma - Post Graduate Institute of Medical Education and ResearchZafar K Khan - Drexel UniversityAjinkya Pattekar - Drexel UniversityVishali Gupta - Post Graduate Institute of Medical Education and ResearchReema Bansal - Post Graduate Institute of Medical Education and ResearchKusum Sharma - Post Graduate Institute of Medical Education and ResearchAshutosh Nath Aggarwal - Post Graduate Institute of Medical Education and ResearchAmod Gupta - Post Graduate Institute of Medical Education and ResearchNaresh Sachdeva - Post Graduate Institute of Medical Education and Research
- Publication Details
- Scientific reports, v 8(1), pp 13812-15
- Publisher
- Springer Nature
- Grant note
- D43 TW009588 / FIC NIH HHS R01 NS097147 / NINDS NIH HHS 3/1/3/JRF-2012/HRD-87 / Indian Council of Medical Research (ICMR) 1R01NS097147 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) BT/01/CEIB/11/02 / Department of Biotechnology, Ministry of Science and Technology (DBT)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000444571200020
- Scopus ID
- 2-s2.0-85053300319
- Other Identifier
- 991019167413504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology