Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection

Espinar-Buitrago, M.S.; Vazquez-Alejo, E.; Magro-Lopez, E.; Tarancon-Diez, L.; Leal, M.; Muñoz-Fernandez, M.A.

doi:10.1016/j.intimp.2023.111103

Cited by 2 publications

(2 citation statements)

References 43 publications

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“…Tα1 has been investigated as an adjuvant therapy for viral, bacterial, and fungal infections ( 33 , 66 , 79 , 80 ). It has been used to treat a variety of illnesses, including chronic hepatitis B and C, ( 81–83 ), acquired immune deficiency syndrome ( 84 ), bacterial and mold pneumonia ( 33 ), sepsis ( 85 , 86 ), and, most recently, COVID-19 ( 80 , 87–103 ).…”

Section: Tα1 In Medicinementioning

confidence: 99%

Phenotypic drug discovery: a case for thymosin alpha-1

Garaci,

Paci,

Matteucci

et al. 2024

Front. Med.

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Phenotypic drug discovery (PDD) involves screening compounds for their effects on cells, tissues, or whole organisms without necessarily understanding the underlying molecular targets. PDD differs from target-based strategies as it does not require knowledge of a specific drug target or its role in the disease. This approach can lead to the discovery of drugs with unexpected therapeutic effects or applications and allows for the identification of drugs based on their functional effects, rather than through a predefined target-based approach. Ultimately, disease definitions are mostly symptom-based rather than mechanism-based, and the therapeutics should be likewise. In recent years, there has been a renewed interest in PDD due to its potential to address the complexity of human diseases, including the holistic picture of multiple metabolites engaging with multiple targets constituting the central hub of the metabolic host–microbe interactions. Although PDD presents challenges such as hit validation and target deconvolution, significant achievements have been reached in the era of big data. This article explores the experiences of researchers testing the effect of a thymic peptide hormone, thymosin alpha-1, in preclinical and clinical settings and discuss how its therapeutic utility in the precision medicine era can be accommodated within the PDD framework.

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Section: Tα1 In Medicinementioning

confidence: 99%

Phenotypic drug discovery: a case for thymosin alpha-1

Garaci,

Paci,

Matteucci

et al. 2024

Front. Med.

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show abstract

“…Particularly, Thymosin-alpha-1 (Tα1) has been shown to play a key role in the control of immunity, tolerance and inflammation, which explains its wide range of clinical applications in several pathologies, including infectious diseases [9]. Recently, we have studied the immunomodulatory effect of Tα1 in a SARS-CoV-2 scenario [10] and during HCMV infection, demonstrating that Tα1 treatment might support its use as an adjuvant for therapeutic treatment with cell therapies or with routine HCMV drugs in immunocompromised patients [11].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

Espinar-Buitrago,

Magro-López,

Vázquez-Alejo

et al. 2024

IJMS

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Resistance and toxicity associated with current treatments for human cytomegalovirus (HCMV) infection highlight the need for alternatives and immunotherapy has emerged as a promising strategy. This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (Tα1) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that Tα1 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFNγ production in T cells and elevated Treg functionality and reduced senescence were evident with Tα1 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with Tα1 + G2S16 treatment. In summary, Tα1 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.

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Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection

Cited by 2 publications

References 43 publications

Phenotypic drug discovery: a case for thymosin alpha-1

Phenotypic drug discovery: a case for thymosin alpha-1

Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection

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