Heterogenous expansion of polymorphonuclear myeloid-derived suppressor cells distinguishes high-risk sepsis immunophenotypes in Uganda

抑制器 髓样 败血症 髓系细胞 髓源性抑制细胞 免疫学 癌症研究 医学 生物 基因 遗传学
作者
Matthew J. Cummings,Vincent Guichard,Nicholas Owor,Thomas Ochar,Moses Kiwubeyi,Rittah Nankwanga,Richard Kibisi,Charles Kassaja,Jesse Ross,Thomas S. Postler,John Kayiwa,Steven J. Reynolds,Martina Cathy Nakibuuka,Joweria Nakaseegu,Julius J. Lutwama,W. Ian Lipkin,Sankar Ghosh,Barnabas Bakamutumaho,Max R. O’Donnell
出处
期刊:Shock [Lippincott Williams & Wilkins]
卷期号:62 (3): 336-343
标识
DOI:10.1097/shk.0000000000002403
摘要

ABSTRACT Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36–59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. Results: Patients who died showed heterogeneous expansion of polymorphonuclear myeloid-derived suppressor cells, with increased and decreased abundance of CD16 − PD-L1 dim and CD16 bright PD-L1 bright subsets, respectively, significantly associated with mortality. While differences between CD16 − PD-L1 dim cell abundance and mortality risk appeared consistent throughout the course of illness, those for the CD16 bright PD-L1 bright subset were more pronounced early after illness onset. Independent of HIV co-infection, depletion of CD4 + T cells, dendritic cells, and CD56 − CD16 bright NK cells were significantly associated with mortality risk, as was expansion of immature, CD56 + CD16 − CD11c + NK cells. Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG-3) was similar between patients who died versus those who survived. Conclusions: This is the first study to define high-risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of myeloid derived suppressor cell expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
李健的小迷弟应助良药采纳,获得10
1秒前
lw777发布了新的文献求助10
1秒前
肖肖发布了新的文献求助10
2秒前
3秒前
3秒前
卡萨卡萨完成签到,获得积分10
7秒前
青松果完成签到,获得积分10
9秒前
yousen完成签到,获得积分20
9秒前
Sid应助Sunwenrui采纳,获得60
9秒前
赘婿应助lw777采纳,获得10
11秒前
12秒前
小蘑菇应助张大英采纳,获得10
12秒前
华仔应助2889580752采纳,获得10
14秒前
嘻嘻完成签到,获得积分10
14秒前
15秒前
丘比特应助科研通管家采纳,获得10
15秒前
领导范儿应助科研通管家采纳,获得10
15秒前
慕青应助科研通管家采纳,获得10
15秒前
15秒前
斯文败类应助科研通管家采纳,获得10
15秒前
15秒前
思源应助科研通管家采纳,获得10
15秒前
田様应助科研通管家采纳,获得10
15秒前
Volcano完成签到,获得积分10
15秒前
无花果应助俏皮的白柏采纳,获得10
16秒前
单薄的夜南应助宁学者采纳,获得10
16秒前
17秒前
17秒前
17秒前
18秒前
空禅yew发布了新的文献求助10
18秒前
华仔应助云辞忧采纳,获得10
20秒前
20秒前
Sunwenrui完成签到,获得积分10
20秒前
12完成签到,获得积分10
22秒前
whoami发布了新的文献求助10
23秒前
23秒前
搜集达人应助TTT0530采纳,获得10
24秒前
张大英发布了新的文献求助10
25秒前
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988868
求助须知:如何正确求助?哪些是违规求助? 3531255
关于积分的说明 11253071
捐赠科研通 3269858
什么是DOI,文献DOI怎么找? 1804822
邀请新用户注册赠送积分活动 881994
科研通“疑难数据库(出版商)”最低求助积分说明 809035