Novel evidence of Thymosin α1 immunomodulatory properties in SARS-CoV-2 infection: Effect on innate inflammatory response in a peripheral blood mononuclear cell-based in vitro model

https://doi.org/10.1016/j.intimp.2023.109996Get rights and content

Highlights

  • SARS-CoV-2 promotes an inflammatory phenotype in human monocytes.

  • In SARS-CoV-2 stimulated PBMC Tα1 mitigates monocyte and myeloid DC activation.

  • Tα1 dampens SARS-CoV-2 mediated induction of pro-inflammatory cytokines.

  • Tα1 promotes release of the anti-inflammatory factors IL-10 from SARS-CoV- 2-stimulated PBMC.

Abstract

The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the “cytokine storm” as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches.

Keywords

SARS-CoV-2
Cytokine
Thymosin α1
Monocyte
Inflammation
Myeloid DC

Abbreviations

Ag
Antigen
Breg
Regulatory B cells
CD
Cluster of Differentiation
COVID-19
Coronavirus Disease 2019
CP
COVID-19 Patient
CP-AS
Asymptomatic COVID-19 Patient
CP-H
Hospitalized COVID-19 Patient
FvDye
Fixable Viability Dye
HD
Healthy Donor
HDT
Host-Directed Therapy
h
Hour
HLA-DR
Human Leukocyte Antigen – D Related Isotype
IFN
Interferon
IL
Interleukin
IQR
Interquartile Range
mAb
Monoclonal Antibody
mDC
Myeloid Dendritic Cells
MFI
Median Fluorescence Intensity
MOI
Multiplicity of Infection
PBMC
Peripheral Blood Mononuclear Cells
pDC
Plasmacytoid Dendritic Cells
SARS-CoV-2
Severe Acute Respiratory Syndrome Coronavirus 2
SD
Standard Deviation
Tα1
Thymosin alpha 1
TCID50
Tissue Culture Infective Dose
TNF
Tumor Necrosis Factor
VOC
Variant of Concern
Yrs
Years

Data availability

No data was used for the research described in the article.

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1

These authors contributed equally.

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