Effects of toll-like receptor agonists and SARS-CoV-2 antigens on interferon (IFN) expression by peripheral blood CD3+ T cells from COVID-19 patients

Samaneh Abdolmohammadi-Vahid, Behzad Baradaran, Armin Sadeghi, Gilina Bezemer, Fatemeh Kiaee, Ian M Adcock, Gert Folkerts, Johan Garssen, Esmaeil Mortaz

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Signaling by toll-like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro. Material & methods: 30 coronavirus disease 2019 (COVID-19) patients (15 severe and 15 moderate) and 10 age and sex-matched healthy control (HC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated and activated with TLR3, 7, 8, and 9 agonists, the spike protein (SP) of SARS-CoV-2, and the receptor binding domain (RBD) of SP. Frequencies of CD3+IFN-β+ T cells, and CD3+IFN-γ+ T cells were evaluated by flow cytometry. Interferon (IFN)-β gene expression was assessed by qRT-PCR. Results: The frequency of CD3+IFN-β+ T cells was higher in PBMCs from moderate (p < 0.0001) and severe (p = 0.009) patients at baseline in comparison with HCs. The highest increase in the frequency of CD3+IFN-β+ T cells in cell from moderate patients was induced by TLR8 agonist and SP (p < 0.0001 for both) when compared to HC, while, the highest increase of the frequency of CD3+IFN-β+ T cells in sample of severe patients was seen with TLR8 and TLR7 agonists (both p = 0.002). The frequency of CD3+IFN-γ+ T cells was significantly increased upon stimulation with TLR agonists in cell from patients with moderate and severe COVID-19, compared with HC (all p < 0.01), except with TLR7 and TLR8 agonists. The TLR8 agonist did not significantly increase the frequency of CD3+IFN-γ+ T cells in PBMCs of severe patients, but did so in cells from patients with moderate disease (p = 0.01). Moreover, IFN-β gene expression was significantly upregulated in CD3+T cells from moderate (p < 0.0001) and severe (p = 0.002) COVID-19 patients, compared to HC after stimulation with the TLR8 agonist, while, stimulation of T cells with SP, significantly up-regulated IFN-β mRNA expression in cells from patients with moderate (p = 0.0003), but not severe disease. Conclusion: Stimulation of PBMCs from COVID-19 patients, especially patients with moderate disease, with TLR8 agonist and SP increased the frequency of IFN-β-producing T cells and IFN-β gene expression.

Original languageEnglish
Article number104897
Number of pages10
JournalExperimental and Molecular Pathology
Volume137
Early online date30 Apr 2024
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 Shahid Beheshti medical University

Funding

This article has been extracted from Ph.D. thesis (number 31611), written by Samaneh Abdolmohammadi-Vahid in School of Medicine, Shahid Beheshti University of Medical Sciences and was supported by a grant of Shahid Beheshti University of Medical sciences, Tehran-Iran (Ethics committee approval ID is: IR.SBMU.MSP.REC.1400.715 and registration number: 14001115). We are grateful to (Clinical Research Development Unit, Imam Reza General Hospital, Tabriz University of Medical Sciences, Tabriz, Iran) for their help in accessing patients' demographic and clinical data.

FundersFunder number
Imam Reza General Hospital
Samaneh Abdolmohammadi-Vahid in School of Medicine , Shahid Beheshti University of Medical Sciences
Samaneh Abdolmohammadi-Vahid in School of Medicine, Shahid Beheshti University of Medical Sciences
Tabriz University of Medical Sciences
Shahid Beheshti University of Medical Sciences14001115

    Keywords

    • COVID-19
    • IFN
    • SARS-CoV-2
    • TLR

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