Anti–PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal Staphylococcus aureus Pneumonia
| Autor: | Cui Xizhong, Junfeng Sun, Yan Li, Lindsay M Busch, Colleen S Curran, Peter Q. Eichacker, Parizad Torabi-Parizi |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Staphylococcus aureus medicine.medical_treatment B7-H1 Antigen Sepsis Mice Major Articles and Brief Reports 03 medical and health sciences 0302 clinical medicine Immune system Intensive care Pneumonia Staphylococcal medicine Animals Immunology and Allergy Lung biology business.industry Bacterial pneumonia Immunotherapy Staphylococcal Infections medicine.disease Disease Models Animal Pneumonia 030104 developmental biology Infectious Diseases medicine.anatomical_structure Immunology biology.protein Antibody business 030215 immunology |
| Zdroj: | J Infect Dis |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Background Staphylococcus aureus (SA) bacterial pneumonia is a common cause of sepsis in intensive care units. Immune checkpoint inhibitors (CPIs) that target programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have been proposed for the treatment of sepsis. However, in our systematic review of sepsis preclinical models, none of the models examined CPIs in pneumonia. Methods Mice were inoculated intratracheally with vehicle control, low dose (LD)- or high dose (HD)-SA. Immune cell recruitment and checkpoint molecule expression were examined at 4, 24, and 48 hours after infection. Infected animals, treated with control or anti–PD-L1 antibodies, were assessed for survival, bacterial burden, lung immunophenotypes, and mediator production. Results LD-SA and HD-SA produced lethality of 15% and 70%, respectively, by 168 hours. At 24 hours, LD-infected animals exhibited increased lung monocyte PD-L1 expression (P = .0002) but lower bacterial counts (P = .0002) compared with HD animals. By 48 hours, either infection induced lung neutrophil and macrophage PD-L1 expression (P Conclusions Anti–PD-L1 therapy did not alter survival in this pneumonia model. Preclinical studies of additional common pathogens and septic foci are needed. |
| Databáze: | OpenAIRE |
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