The COVID-19 pandemic is an ongoing global pandemic of coronavirus disease 2019 as an atypical type of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many potential pharmacotherapies are currently being investigated against this disease. This article points to and justifies, the importance of investigating the potential therapeutic value of pharmacological agents acting on Toll-like Receptor (TLR) 7 and/or TLR8 as double-edged swords combating COVID-19. Induction of TLR7 and/or TLR8 may be investigated as a strategy to stimulate immunity and may be added to anti-COVID19 vaccines to cope with their current viral escape challenge. TLR7 stimulation may not only help viral clearance through Th1 antiviral responses but may also provide beneficial broncho- and vaso-dilatory, as well as, anti-inflammatory effects. Pharmacological compounds acting as TLR7 and/or TLR8 agonists may be of value if used by frontline healthcare workers with comorbidities who demonstrate mild symptoms of the disease. On the other hand, TLR7 and/or TLR8 antagonists may be used in combination with immune-modulatory/anti-inflammatory drugs in severe cases of the disease, with potential synergistic effects that could also help in reducing the doses of such therapies, and consequently their adverse effects.
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http://dx.doi.org/10.1016/j.crphar.2021.100068 | DOI Listing |
Viruses
December 2024
Instituto René Rachou/Fiocruz Minas, Belo Horizonte 30190-009, MG, Brazil.
The global number of COVID-19 deaths has reached 7 million, with 4% of these deaths occurring in children and adolescents. In Brazil, around 1500 children up to 11 years old died from the disease. The most common symptoms in children are respiratory, potentially progressing to severe illnesses, such as severe acute respiratory syndrome (SARS) and MIS-C.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
Endosomal toll-like receptors (TLRs) TLR7, TLR8, and TLR9 play an important role in systemic lupus erythematosus (SLE) pathogenesis. The proteolytic processing of these receptors in the endolysosome is required for signaling in response to DNA and single-stranded RNA, respectively. Targeting this proteolytic processing may represent a novel strategy to inhibit TLR-mediated pathogenesis.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged.
View Article and Find Full Text PDFJ Exp Med
March 2025
Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recognition through unknown mechanisms, as patients deficient in RNase T2 suffer from neuroinflammation.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
Human rhinovirus C (HRV-C) is a significant contributor to respiratory tract infections in children and is implicated in asthma exacerbations across all age groups. Despite its impact, there is currently no licensed vaccine available for HRV-C. Here, we present a novel approach to address this gap by employing immunoinformatics techniques for the design of a multi-epitope-based vaccine against HRV-C.
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