Variant rs4986790 of toll-like receptor 4 affects the signaling and induces cell dysfunction in patients with severe COVID-19
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
OBJECTIVES: We investigated the expression of toll-like receptor (TLR)-4 on the cell surface of innate and adaptive cells from patients with COVID-19 carrying the rs4986790 GG genotype in the TLR4 gene and the functional profile of these cells.
METHODS: We included 1169 hospitalized patients with COVID-19. The rs4986790 in TLR4 was identified by real-time polymerase chain reaction. Peripheral blood mononuclear cells were isolated and cultured to evaluate TLR-4 expression on immune cells. Supernatants recovered culture assays were stored, and we measured cytokines and cytotoxic molecules.
RESULTS: We showed that the rs4986790 (GG) was significantly associated (P = 0.0310) with severe COVID-19. Cells of patients with COVID-19 carrying the GG genotype have increased the frequency of monocytes and activated naïve and non-switched B cells positive to TLR-4 when cells are stimulated with lipopolysaccharide and with spike protein of SARS-CoV-2. Also, cells from patients with GG COVID-19 cannot produce pro-inflammatory cytokines after lipopolysaccharide stimulus, but they are high producers of cytotoxic molecules at baseline.
CONCLUSIONS: The rs4986790 GG genotype of the TLR4 is associated with the risk of COVID-19 and acute respiratory distress syndrome. Peripheral blood mononuclear cells of patients carrying the rs4986790 (TLR4) GG genotype had a limited delivery of pro-inflammatory cytokines compared to the AA and AG genotypes in which TLR-4 stimulation induces IL-10, IL-6, tumor necrosis factor-α, and Fas ligand production.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
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| Enthalten in: |
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases - 138(2024) vom: 29. Jan., Seite 102-109 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Flores-Gonzalez, Julio [VerfasserIn] |
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| Links: |
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| Themen: |
B cell |
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| Anmerkungen: |
Date Completed 31.01.2024 Date Revised 31.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijid.2023.11.032 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365209759 |
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| 100 | 1 | |a Flores-Gonzalez, Julio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Variant rs4986790 of toll-like receptor 4 affects the signaling and induces cell dysfunction in patients with severe COVID-19 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a OBJECTIVES: We investigated the expression of toll-like receptor (TLR)-4 on the cell surface of innate and adaptive cells from patients with COVID-19 carrying the rs4986790 GG genotype in the TLR4 gene and the functional profile of these cells | ||
| 520 | |a METHODS: We included 1169 hospitalized patients with COVID-19. The rs4986790 in TLR4 was identified by real-time polymerase chain reaction. Peripheral blood mononuclear cells were isolated and cultured to evaluate TLR-4 expression on immune cells. Supernatants recovered culture assays were stored, and we measured cytokines and cytotoxic molecules | ||
| 520 | |a RESULTS: We showed that the rs4986790 (GG) was significantly associated (P = 0.0310) with severe COVID-19. Cells of patients with COVID-19 carrying the GG genotype have increased the frequency of monocytes and activated naïve and non-switched B cells positive to TLR-4 when cells are stimulated with lipopolysaccharide and with spike protein of SARS-CoV-2. Also, cells from patients with GG COVID-19 cannot produce pro-inflammatory cytokines after lipopolysaccharide stimulus, but they are high producers of cytotoxic molecules at baseline | ||
| 520 | |a CONCLUSIONS: The rs4986790 GG genotype of the TLR4 is associated with the risk of COVID-19 and acute respiratory distress syndrome. Peripheral blood mononuclear cells of patients carrying the rs4986790 (TLR4) GG genotype had a limited delivery of pro-inflammatory cytokines compared to the AA and AG genotypes in which TLR-4 stimulation induces IL-10, IL-6, tumor necrosis factor-α, and Fas ligand production | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Falfán-Valencia, Ramcés |e verfasserin |4 aut | |
| 700 | 1 | |a Roldán, Ivette Buendía |e verfasserin |4 aut | |
| 700 | 1 | |a Fricke-Galindo, Ingrid |e verfasserin |4 aut | |
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| 700 | 1 | |a Guzmán-Guzmán, Iris Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Rubio, Gloria |e verfasserin |4 aut | |
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