Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response
García Vidal, Edurne (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Calba, Ignasi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Riveira Muñoz, Eva (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
García Rodríguez, Elisabet (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Serra Mitjà, Pere (Institut d'Investigació Biomèdica Sant Pau)
Cabrera Navarro, Cecilia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ballana, Ester (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Badia, Roger (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells.
Ajuts:	Instituto de Salud Carlos III PI22/01575
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	NOD-like receptor ; SARS-CoV-2 ; Innate immunity ; Respiratory mucosa ; Viral respiratory infections
Publicat a:	International journal of molecular sciences, Vol. 25 Núm. 10 (may 2024) , p. 5318, ISSN 1422-0067

DOI: 10.3390/ijms25105318
PMID: 38791357

17 p, 2.7 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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