Augmented Innate and Adaptive Immune Responses Under Conditions of Diabetes-Filariasis Comorbidity.

Joy Manohar Sibi,Viswanathan Mohan,Vivekanandhan Aravindhan,Saravanan Munisankar,Subash Babu

doi:10.3389/fimmu.2021.716515

Abstract

Metainflammation, as seen in chronic diabetes subjects, impairs immunity and increases the susceptibility to infections. In the present study, the effect of diabetes on immune response against filariasis was studied. Both toll-like receptor (TLR)-mediated and crude antigen-induced immune responses were quantified, in whole blood cultures from filariasis-infected subjects (LF+), with and without diabetes. Blood cultures were stimulated with TLR ligands (TLR2 and TLR4) or filarial antigen or were left unstimulated (control) for 18 h. Cytokine, chemokine, and defensin secretion was quantified by ELISA. Expression of HLA-DR, B7-1, B7-2, activation marker (CD69), and Th (Th1, Th2, Th17, and Th9) phenotypes was quantified by flow cytometry. Expression of immunomodulatory effectors (Cox-2, HO-1, IDO-1, and p47Phox) and Th-polarizing transcription factors (T-bet, GATA3, and ROR-γt) was quantified by quantitative PCR. Secretion of IL-27, IL-1Ra, IL-12, IL-33, IL-9, and SDF-1 was increased under diabetes conditions with increased Th9 polarization and increased expression of Cox-2 and IDO. Overall, diabetes was found to augment both TLR-mediated and antigen-induced inflammation, which can promote chronic pathology in LF+ subjects.

Highlights

Filarial infections, unlike viral and bacterial infections, induce immunomodulation, rather than inflammation [1]
TLR2 stimulation resulted in the secretion of tumor necrosis factor-alpha (TNF-a), IL-6, IL-1b, and IL-10
TLR4 stimulation resulted in the secretion of TNF-a, IL-6, IL1b, IL-10, and IL-27

Summary

Introduction

Unlike viral and bacterial infections, induce immunomodulation, rather than inflammation [1]. Murine studies have shown significant protection against both forms of diabetes (type 1 and type 2) by filarial pre-infections [2,3,4]. Diabetes and Filariasis Co-Morbidity subjects [6]. This effect was specific only to T1DM and T2DM and was not seen in those with coronary artery disease (CAD) [7]. These observations were later replicated in other Asian countries like China [8] and Indonesia [9]

Methods

Results

Conclusion