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Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury.
J Leukoc Biol. 2018 01; 103(1):23-33.JL

Abstract

Burn patients are susceptible to infections due, in part, to immune dysfunction. Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to immune dysfunction after burn injury. To determine the impact of burn injury and infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and its relationship to T cell functions. The efficacy of anti-PD-L1 antibody was evaluated in a clinically relevant mouse model of burn injury and bacterial infection. Mice underwent 35% scald burn followed by Pseudomonas aeruginosa or Staphylococcus aureus infection on day 4 postburn. Anti-PD-L1 was administered on day 3 postburn. Numbers and phenotype of leukocytes, plasma cytokine concentrations, bacterial clearance, organ injury, and survival were assessed. Burn injury and infection with P. aeruginosa caused a significant upregulation of PD-L1 on myeloid cells, along with a decrease in T cell numbers and function, significant multiorgan injury, and decreased survival. Treatment with anti-PD-L1 antibody improved bacterial clearance, reduced organ injury, and enhanced survival during Pseudomonas burn wound infection. Furthermore, anti-PD-L1 effectively protected against multiorgan injury, and improved bacterial clearance and survival following systemic S. aureus infection after burn injury. Blockade of PD-1/PD-L1 interactions might represent a viable treatment to improve outcomes among critically ill burn-injured subjects and increased leukocyte PD-L1 expression could serve as a valuable biomarker to select appropriate patients for such treatment.

Authors+Show Affiliations

Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29345058

Citation

Patil, Naeem K., et al. "Frontline Science: Anti-PD-L1 Protects Against Infection With Common Bacterial Pathogens After Burn Injury." Journal of Leukocyte Biology, vol. 103, no. 1, 2018, pp. 23-33.
Patil NK, Luan L, Bohannon JK, et al. Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury. J Leukoc Biol. 2018;103(1):23-33.
Patil, N. K., Luan, L., Bohannon, J. K., Hernandez, A., Guo, Y., & Sherwood, E. R. (2018). Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury. Journal of Leukocyte Biology, 103(1), 23-33. https://doi.org/10.1002/JLB.5HI0917-360R
Patil NK, et al. Frontline Science: Anti-PD-L1 Protects Against Infection With Common Bacterial Pathogens After Burn Injury. J Leukoc Biol. 2018;103(1):23-33. PubMed PMID: 29345058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury. AU - Patil,Naeem K, AU - Luan,Liming, AU - Bohannon,Julia K, AU - Hernandez,Antonio, AU - Guo,Yin, AU - Sherwood,Edward R, Y1 - 2017/12/21/ PY - 2017/09/05/received PY - 2017/10/13/revised PY - 2017/10/25/accepted PY - 2018/1/19/entrez PY - 2018/1/19/pubmed PY - 2019/4/16/medline KW - T cells KW - burn injury KW - checkpoint receptors KW - infection KW - myeloid cells KW - sepsis SP - 23 EP - 33 JF - Journal of leukocyte biology JO - J. Leukoc. Biol. VL - 103 IS - 1 N2 - Burn patients are susceptible to infections due, in part, to immune dysfunction. Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to immune dysfunction after burn injury. To determine the impact of burn injury and infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and its relationship to T cell functions. The efficacy of anti-PD-L1 antibody was evaluated in a clinically relevant mouse model of burn injury and bacterial infection. Mice underwent 35% scald burn followed by Pseudomonas aeruginosa or Staphylococcus aureus infection on day 4 postburn. Anti-PD-L1 was administered on day 3 postburn. Numbers and phenotype of leukocytes, plasma cytokine concentrations, bacterial clearance, organ injury, and survival were assessed. Burn injury and infection with P. aeruginosa caused a significant upregulation of PD-L1 on myeloid cells, along with a decrease in T cell numbers and function, significant multiorgan injury, and decreased survival. Treatment with anti-PD-L1 antibody improved bacterial clearance, reduced organ injury, and enhanced survival during Pseudomonas burn wound infection. Furthermore, anti-PD-L1 effectively protected against multiorgan injury, and improved bacterial clearance and survival following systemic S. aureus infection after burn injury. Blockade of PD-1/PD-L1 interactions might represent a viable treatment to improve outcomes among critically ill burn-injured subjects and increased leukocyte PD-L1 expression could serve as a valuable biomarker to select appropriate patients for such treatment. SN - 1938-3673 UR - https://www.unboundmedicine.com/medline/citation/29345058/Frontline_Science:_Anti_PD_L1_protects_against_infection_with_common_bacterial_pathogens_after_burn_injury_ L2 - https://doi.org/10.1002/JLB.5HI0917-360R DB - PRIME DP - Unbound Medicine ER -