TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinu
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Microbial Cell Factories Open Access
RESEARCH
TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis Gargi Rai1, Shukla Das1* , Mohammad Ahmad Ansari1, Praveen Kumar Singh1, Sajad Ahmad Dar1,2, Shafiul Haque2, Neelima Gupta3, Sonal Sharma4, Vishnampettai Ganapathysubramanian Ramachandran1, Sanskriti Sharma5, Charu Jain6 and Shipra Sharma7
Abstract Background: T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. Results: The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-β levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. Conclusions: Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease. Keywords: Chronic rhinosinusitis, Nasal polyposis, T helper 17, T regulatory cells, Toll-like receptor, Aspergillus flavus
*Correspondence: [email protected] 1 Department of Microbiology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India Full list of author information is available at the end of the article
Background Chronic rhinosinusitis with nasal polyps (CRSwNP), a subgroup of chronic rhinosinusitis (CRS), is clinically described by the presence of nasal polyps detectable to the clinician through nasal endoscopy. Nasal congestion, loss of smell, hyposmia and facial pressure are the common clinic
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