COVID-19 patients with high TNF/IFN-γ levels show hallmarks of PANoptosis, an inflammatory cell death.

Autor: Palacios Y; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Ramón-Luing LA; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Ruiz A; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., García-Martínez A; Hospital Central Militar, SEDENA, Mexico City 11200, Mexico., Sánchez-Monciváis A; Laboratorio de Inmunología, Escuela Militar de Graduados de Sanidad, SEDENA, Mexico City 11200, Mexico., Barreto-Rodríguez O; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Falfán-Valencia R; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Pérez-Rubio G; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Medina-Quero K; Laboratorio de Inmunología, Escuela Militar de Graduados de Sanidad, SEDENA, Mexico City 11200, Mexico., Buendia-Roldan I; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico., Chavez-Galan L; Instituto Nacional de Enfermedades Respiratorias 'Ismael Cosío Villegas', Mexico City 14080, Mexico. Electronic address: lchavez_galan@iner.gob.mx.
Jazyk: angličtina
Zdroj: Microbes and infection [Microbes Infect] 2023 Nov-Dec; Vol. 25 (8), pp. 105179. Date of Electronic Publication: 2023 Jun 30.
DOI: 10.1016/j.micinf.2023.105179
Abstrakt: TNF and IFN-γ trigger cell damage during SARS CoV-2 infection; these cytokines can induce senescence and a cell death process called PANoptosis. This study included 138 vaccine-naïve COVID-19 patients, who were divided into four groups (Gp) according to the plasma level of TNF and IFN-γ (High [ Hi ] or Normal-Low [ No-Low ]), Gp 1: TNF Hi /IFNγ Hi ; Gp 2: TNF Hi /IFNγ No-Low ; Gp 3: TNF No-Low /IFNγ Hi ; and Gp 4: TNF No-Low /IFNγ No-Low . Thirty-five apoptosis-related proteins and molecules related to cell death and senescence were evaluated. Our results showed that groups did not display differences in age and comorbidities. However, 81% of the Gp 1 patients had severe COVID-19, and 44% died. Notably, the p21/CDKN1A was increased in Gp 2 and Gp 3. Moreover, Gp 1 showed higher TNFR1, MLKL, RIPK1, NLRP3, Caspase 1, and HMGB-1 levels, suggesting elevated TNF and IFN-γ levels simultaneously activate diverse cell death pathways because it is not observed when only one of these cytokines is increased. Thus, high TNF/IFN-γ levels are predominant in severe COVID-19 status, and patients display cell alterations associated with the activation of diverse cell death pathways, including a possible senescent phenotype.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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