A novel role for coinhibitory receptors/checkpoint proteins in the immunopathology of sepsis

作者:Fallon Eleanor A; Biron Girard Bethany M; Chung Chun Shiang; Lomas Neira Joanne; Heffernan Daithi S; Monaghan Sean F; Ayala Alfred*
来源:Journal of Leukocyte Biology, 2018, 103(6): 1151-1164.
DOI:10.1002/JLB.2MIR0917-377R

摘要

Coinhibitory molecules, such as PD-1, CTLA-4, 2B4, and BTLA, are an important new family of mediators in the pathophysiology of severe bacterial and/or fungal infection, as well as the combined insults of shock and sepsis. Further, the expression of these molecules may serve as indicators of the immune status of the septic individual. Using PD-1:PD-L as an example, we discuss in this review how such checkpoint molecules may affect the host response to infection by mediating the balance between effective immune defense and immune-mediated tissue injury. Additionally, we explore how the up-regulation of PD-1 and/or PD-L1 expression on not only adaptive immune cells (e.g., T cells), but also on innate immune cells (e.g., macrophages, monocytes, and neutrophils), as well as nonimmune cells during sepsis and/or shock contributes to functional alterations often with detrimental sequelae.

  • 出版日期2018-6