Identification and characterization of neutrophil heterogeneity in sepsis.
Crit Care
; 25(1): 50, 2021 02 06.
Article
em En
| MEDLINE
| ID: mdl-33549126
ABSTRACT
BACKGROUND:
Although the immune function of neutrophils in sepsis has been well described, the heterogeneity of neutrophils remains unclear during the process of sepsis.METHODS:
In this study, we used a mouse CLP model to simulate the clinical scenario of patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS was used to stimulate neutrophils in vitro to simulate sepsis; single-cell gene sequencing technology was used to explore the immunological typing. To explore the immunological function of immunosuppressive neutrophils, PD-L1 knockout neutrophils were cocultured with lymphocytes from wild-type mice.RESULTS:
We found that neutrophils presented variant dysfunction at the late stage of sepsis, including inhibition of apoptosis, seriously damaged chemotaxis and extensive infiltration into the tissues. Single-cell RNA sequencing revealed that multiple subclusters of neutrophils were differentiated after LPS stimulation. The two-dimensional spatial distribution analysis showed that Foxp3+ T cells were much closer to Ly-6G than the CD4+ and CD8+ cells, indicating that infiltrated neutrophils may play immunomodulatory effect on surrounding T-regs. Further observations showed that LPS mediates PD-L1 over expression through p38α-MSK1/-MK2 pathway in neutrophils. The subsets of highly expressed PD-L1 exert immunosuppressive effect under direct contact mode, including inhibition of T cell activation and induction of T cell apoptosis and trans-differentiation.CONCLUSIONS:
Taken together, our data identify a previously unknown immunosuppressive subset of neutrophils as inhibitory neutrophil in order to more accurately describe the phenotype and characteristics of these cells in sepsis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sepse
/
Heterogeneidade Genética
/
Neutrófilos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article