Up-regulation of Programmed Cell Death 1 Ligand 1 on Neutrophils May Be Involved in Sepsis-induced Immunosuppression

Wang, Jiafeng; Li, Jinbao; Zhao, Yanjun; Yi, Wen-Jing; Bian, Jinjun; Wan, Xiaojian; Zhu, Keming; Deng, Xiaoming

doi:10.1097/aln.0000000000000525

Cited by 90 publications

(94 citation statements)

References 33 publications

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“…Moreover neutrophils harvested from patients who have sustained sepsis or multiple trauma can induce the apoptotic death of other cells through the dephosphorylation of epithelial cell caspase-8 (38). Expression of PDL-1 is increased on septic neutrophils, and through interactions with lymphocyte PD-1, can induce the apoptotic death of CD4+ lymphocytes (39). …”

Section: Resultsmentioning

confidence: 99%

Immune Cell Phenotype and Function in Sepsis

Rimmelé

Payen²,

Cantaluppi³

et al. 2016

Shock

129

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Cells of the innate and adaptive immune systems play a critical role in the host response to sepsis. Moreover, their accessibility for sampling and their capacity to respond dynamically to an acute threat increases the possibility that leukocytes might serve as a measure of a systemic state of altered responsiveness in sepsis. The working group of the 14th Acute Dialysis Quality Initiative (ADQI) conference sought to obtain consensus on the characteristic functional and phenotypic changes in cells of the innate and adaptive immune system in the setting of sepsis. Techniques for the study of circulating leukocytes were also reviewed and the impact on cellular phenotypes and leukocyte function of non extracorporeal treatments and extracorporeal blood purification therapies proposed for sepsis was analyzed. A large number of alterations in the expression of distinct neutrophil and monocyte surface markers have been reported in septic patients. The most consistent alteration seen in septic neutrophils is their activation of a survival program that resists apoptotic death. Reduced expression of HLA-DR is a characteristic finding on septic monocytes but monocyte antimicrobial function does not appear to be significantly altered in sepsis. Regarding adaptive immunity, sepsis-induced apoptosis leads to lymphopenia in patients with septic shock and it involves all types of T cells (CD4, CD8 and Natural Killer) except T regulatory cells, thus favoring immunosuppression. Finally, numerous promising therapies targeting the host immune response to sepsis are under investigation. These potential treatments can have an effect on the number of immune cells, the proportion of cell subtypes and the cell function.

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Section: Resultsmentioning

confidence: 99%

Immune Cell Phenotype and Function in Sepsis

Rimmelé

Payen²,

Cantaluppi³

et al. 2016

Shock

129

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“…Patients with severe sepsis show increased levels of PD-1 and PD-L1 on their monocyte and T lymphocyte populations (116). Recent studies demonstrated neutrophil PD-L1 upregulation on neutrophils from septic mice and humans, resulting in the potentiation of lymphocyte apoptosis through contact inhibition, which correlated with outcome (117). Moreover, in clinically relevant animal models of bacterial sepsis, inhibition of PD-1 and PD-L1 signaling improved survival and reduced the incidence of fungal infections (118).…”

Section: Potential Immune-modulatory Therapiesmentioning

confidence: 99%

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Delano¹,

Ward²

2016

Journal of Clinical Investigation

476

444

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Sepsis affects the immune system by directly altering the lifespan, production, and function of the effector cells responsible for Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.

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“…The myeloid-derived dendritic cells increase their expression of PD-L1 in response to dsRNA [17, 18, 31]. Recent investigations revealed that there are different neutrophil subsets in mice and humans [32–34]. A CD16 high /CD62L dim subset is known to suppress lymphocyte proliferation and induces lymphocyte apoptosis, through PD-L1 expression on this subset [33, 34].…”

Section: Discussionmentioning

confidence: 99%

“…Recent investigations revealed that there are different neutrophil subsets in mice and humans [32–34]. A CD16 high /CD62L dim subset is known to suppress lymphocyte proliferation and induces lymphocyte apoptosis, through PD-L1 expression on this subset [33, 34]. These studies raise a possibility that suppression of PD-L1 expression in CIC/IND-treated mice may be partly due to downregulation of PD-L1 on the neutrophil subset.…”

Section: Discussionmentioning

confidence: 99%

“…The upregulation of PD-L1 on epithelial cells render virus-specific CTLs to fail to eradicate virus-infected epithelial cells [14, 15]. The upregulation of PD-L1 on myeloid-derived inflammatory cells, particularly the neutrophil subset described above, suppress lymphocyte proliferation, induce lymphocyte apoptosis, and then compromise anti-pathogen host defense [34, 36]. With this regard, ICS/LABA treatment may be beneficial for earlier virus eradication.…”

Section: Discussionmentioning

confidence: 99%

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Effects of corticosteroid plus long-acting beta2-agonist on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice

et al. 2017

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BackgroundAirway viral infections cause the exacerbations of asthma and chronic obstructive pulmonary disease. PD-L1, also known as B7-H1, is an immune-checkpoint molecule that plays a role in an escape mechanism of viruses from the host immune systems. This escape may be associated with the persistence of viral infection and the exacerbation of the underlying diseases. In a study in vitro, we have shown that corticosteroids plus long-acting beta2-agonists (LABAs) attenuate the upregulation of PD-L1 on airway epithelial cells stimulated with an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C). To address its biological relevance in vivo, we investigated the effect of corticosteroid plus LABA on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice.MethodsMice were intratracheally administered with poly I:C. The expression of PD-L1 on the lung cells was assessed by flow cytometry and inflammation was assessed for bronchoalveolar lavage fluid (BALF). Independent as well as combination effects of ciclesonide and indacaterol were examined.ResultsAdministration of low dose poly I:C upregulated the expression of PD-L1, induced neutrophilia and increased keratinocyte-derived chemokine (KC), macrophage inflammatory protein-1β (MIP-1β), and IL-6 in BALF. The upregulation of PD-L1, neutrophilic inflammation and increase of KC were suppressed by ciclesonide plus indacaterol, but not by either when administered independently. Although the upregulation of PD-L1 by high dose poly I:C was suppressed by ciclesonide plus indacaterol, neutrophilia and increased KC, MIP-1β, and IL-6 in BALF were not attenuated.ConclusionsCiclesonide plus indacaterol attenuate double-stranded RNA-induced upregulation of PD-L1 in the lungs.

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Up-regulation of Programmed Cell Death 1 Ligand 1 on Neutrophils May Be Involved in Sepsis-induced Immunosuppression

Abstract: PD-L1 is up-regulated on neutrophils during sepsis, which may be related to sepsis-induced immunosuppression.

Cited by 90 publications

References 33 publications

Immune Cell Phenotype and Function in Sepsis

Immune Cell Phenotype and Function in Sepsis

Sepsis-induced immune dysfunction: can immune therapies reduce mortality?

Effects of corticosteroid plus long-acting beta2-agonist on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice

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