作者
Lukose K Thampy, Kenneth E Remy, Andrew H Walton, Zachery Hong, Kelilah Liu, Rebecca Liu, Victoria Yi, Carey-Ann D Burnham, Richard S Hotchkiss
发表日期
2018/6/26
期刊
PLoS One
卷号
13
期号
6
页码范围
e0199497
出版商
Public Library of Science
简介
Background
Multidrug resistant (MDR) bacterial pathogens are a serious problem of increasing importance facing the medical community. MDR bacteria typically infect the most immunologically vulnerable: patients in intensive care units, patients with extensive comorbidities, oncology patients, hemodialysis patients, and other immune suppressed individuals are likely to fall victim to these pathogens. One promising novel approach to treatment of MDR bacteria is immuno-adjuvant therapy to boost patient immunity. Success with this strategy would have the major benefit of providing protection against a number of MDR pathogens.
Objectives
This study had two main objectives. First, immunophenotyping of peripheral blood mononuclear cells from patients with sepsis associated with MDR bacteria was performed to examine for findings indicative of immunosuppression. Second, the ability of three immuno-adjuvants with distinct mechanisms of action to reverse CD4 and CD8 T cell dysfunction, a pathophysiological hallmark of sepsis, was evaluated.
Results
Septic patients with MDR bacteria had increased expression of the inhibitory receptor PD-1 and its ligand PD-L1 and decreased monocyte HLA-DR expression compared to non-septic patients. All three immuno-adjuvants, IL-7, anti-PD-L1, and OX-40L, increased T cell production of IFN-γ in a subset of septic patients with MDR bacteria: IL-7 was most efficacious. There was a strong trend toward increased mortality in patients whose T cells failed to increase IFN-γ production in response to the three treatments.
Conclusion
Immuno-adjuvant therapy reversed T cell dysfunction, a key …
学术搜索中的文章
LK Thampy, KE Remy, AH Walton, Z Hong, K Liu, R Liu… - PLoS One, 2018