tetano
Editor, Senior Moderator
J Leukoc Biol
. 2024 Nov 28:qiae252.
doi: 10.1093/jleuko/qiae252. Online ahead of print. Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection
Shamik Majumdar[SUP] 1 [/SUP], Joseph D Weaver[SUP] 1 [/SUP], Sergio M Pontejo[SUP] 1 [/SUP], Mahnaz Minai[SUP] 2 [/SUP], Xinping Lu[SUP] 3 [/SUP], Ji-Liang Gao[SUP] 1 [/SUP], Gibran Holmes[SUP] 3 [/SUP], Reed Johnson[SUP] 4 [/SUP], Hongwei Zhang[SUP] 3 [/SUP], Brian L Kelsall[SUP] 5 [/SUP], Joshua M Farber[SUP] 3 [/SUP], Derron A Alves[SUP] 2 [/SUP], Philip M Murphy[SUP] 1 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction and virus load in the lungs of male mice were not broadly influenced by Cxcl10 deficiency. However, accumulation of B and T lymphocytes in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19.
Keywords: COVID-19; chemokine; chemokine receptor; cytokine; lymphocytes.
. 2024 Nov 28:qiae252.
doi: 10.1093/jleuko/qiae252. Online ahead of print. Cxcl10 is protective during mouse-adapted SARS-CoV-2 infection
Shamik Majumdar[SUP] 1 [/SUP], Joseph D Weaver[SUP] 1 [/SUP], Sergio M Pontejo[SUP] 1 [/SUP], Mahnaz Minai[SUP] 2 [/SUP], Xinping Lu[SUP] 3 [/SUP], Ji-Liang Gao[SUP] 1 [/SUP], Gibran Holmes[SUP] 3 [/SUP], Reed Johnson[SUP] 4 [/SUP], Hongwei Zhang[SUP] 3 [/SUP], Brian L Kelsall[SUP] 5 [/SUP], Joshua M Farber[SUP] 3 [/SUP], Derron A Alves[SUP] 2 [/SUP], Philip M Murphy[SUP] 1 [/SUP]
Affiliations
- PMID: 39607906
- DOI: 10.1093/jleuko/qiae252
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, remains endemic worldwide. Circulating levels of the chemokine CXCL10 are strongly positively associated with poor outcome; however, its precise role in SARS-CoV-2 pathogenesis and its suitability as a therapeutic target have remained undefined. Here, we challenged mice genetically deficient in Cxcl10 with a mouse-adapted strain of SARS-CoV-2. Infected male, but not female, Cxcl10-/- mice displayed increased mortality compared to wild type controls. Histopathological damage, inflammatory gene induction and virus load in the lungs of male mice were not broadly influenced by Cxcl10 deficiency. However, accumulation of B and T lymphocytes in the lung parenchyma of infected mice was reduced in the absence of Cxcl10. Thus, during acute SARS-CoV-2 infection, Cxcl10 regulates lymphocyte infiltration in lung and confers protection against mortality. Our preclinical model results do not support targeting CXCL10 therapeutically in severe COVID-19.
Keywords: COVID-19; chemokine; chemokine receptor; cytokine; lymphocytes.