p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus

Menéndez, Daniel; Snipe, Joyce; Marzec, Jacqui; Innes, Cynthia L.; Polack, Fernando P.; Caballero, Mauricio T.; Schurman, Shepherd H.; Kleeberger, Steven R.; Resnick, Michael A.

doi:10.1172/jci128626

Cited by 26 publications

(21 citation statements)

References 64 publications

(84 reference statements)

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“…After induction of p53 and incubation with single-stranded RNA ligands in human primary lymphocytes, SNP-dependent IL-6 expression, TLR8 expression and p53 binding were all increased. 147 Variation in TLR4 also associates with severe RSV disease, although this has not been replicated in all cohorts. 56 Two SNPs encoding Asp299Gly and Thr399Ile substitutions in the TLR4 ectodomain, previously associated with TLR4 hypo-responsiveness to lipopolysaccharide (LPS), were represented at higher frequencies in children with symptomatic RSV disease.…”

Section: Influence Of Genetic Variation On Viral-induced Inflammationmentioning

confidence: 98%

Genetic influences on viral-induced cytokine responses in the lung

Forbester

Humphreys

2021

Mucosal Immunology

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Section: Influence Of Genetic Variation On Viral-induced Inflammationmentioning

confidence: 98%

Genetic influences on viral-induced cytokine responses in the lung

Forbester

Humphreys

2021

Mucosal Immunology

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“…Functional loss of P53 due to RSV infection was correlated to NF-kB activity via the NS-1/NS2-PI3K/Akt pathway [ 155 ]. Moreover, P53 induced the expression of toll-like receptor 8 (TLR8), which is associated with RSV infection and enhances the TLR8-mediated immune responses [ 156 ].…”

Section: Copdmentioning

confidence: 99%

P53 in the impaired lungs

Uddin

Barabutis

2020

DNA Repair

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Our laboratory is focused on investigating the supportive role of P53 towards the maintenance of lung homeostasis. Acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, pulmonary arterial hypertension, pneumonia and tuberculosis are respiratory pathologies, associated with dysfunctions of this endothelium defender (P53). Herein we review the evolving role of P53 towards the aforementioned inflammatory disorders, to potentially reveal new therapeutic possibilities in pulmonary disease.

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“…The TLR7 and 8 genes display copy number variation (CNV) in the population (Wang et al 2014). In addition, TLR genes display allelic polymorphisms (Menendez et al 2019;Wang et al 2014) that may influence the strength of the interaction with their respective ligands or the quality of the ensuing signal that is transduced to the nucleus. There is ample proof that gender-based CNV of TLR7 has medical implications.…”

mentioning

confidence: 99%