Format

Send to

Choose Destination
Int J Mol Sci. 2017 Nov 14;18(11). pii: E2413. doi: 10.3390/ijms18112413.

Targeting Immune Cell Checkpoints during Sepsis.

Author information

1
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. naeem.patil@vanderbilt.edu.
2
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. yin.guo.1@vanderbilt.edu.
3
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. liming.luan@vanderbilt.edu.
4
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. edward.r.sherwood@vanderbilt.edu.
5
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. edward.r.sherwood@vanderbilt.edu.

Abstract

Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis. Engagement of these inhibitory molecules on various immune cells has been consistently shown to inhibit innate immune cell functions (e.g., phagocytosis, cytokine production and pathogen clearance) and also lead to impaired T cell competence. In numerous pre-clinical models of sepsis, therapeutic agents aimed at blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival. Therefore, immunotherapy with immune cell checkpoint inhibitors holds significant potential for the future of sepsis therapy and merits further investigation.

KEYWORDS:

2B4; BTLA; CTLA-4; LAG-3; PD-1; PD-L1; T cell exhaustion; TIM-3; immunosuppression; immunotherapy; myeloid cells; sepsis

PMID:
29135922
PMCID:
PMC5713381
DOI:
10.3390/ijms18112413
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center