Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation

Köffel, René; Meshcheryakova, Anastasia; Warszawska, Joanna; Hennig, Annika; Wagner, Karin; Jörgl, Almut; Gubi, Daniela; Moser, Doris; Hladik, Anastasiya; Hoffmann, Ulrich; Fischer, Michael B.; Berg, W. van den; Koenders, Marije I.; Scheinecker, Clemens; Geßlbauer, Bernhard; Knapp, Sylvia; Strobl, Herbert

doi:10.1182/blood-2014-07-588178

Cited by 41 publications

(40 citation statements)

References 64 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent evidence suggests that the immature neutrophils seen in the circulation during sepsis can undergo differentiation to become monocytic cells (27), underlining the plasticity of myeloid cell responses to an acute threat, and the challenges of ascribing distinct biologic responses to discrete cellular phenotypes in sepsis. Two alterations in cellular phenotype merit special mention.…”

Section: Resultsmentioning

confidence: 99%

Immune Cell Phenotype and Function in Sepsis

Rimmelé

Payen²,

Cantaluppi³

et al. 2016

Shock

133

114

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Immune Cell Phenotype and Function in Sepsis

Rimmelé

Payen²,

Cantaluppi³

et al. 2016

Shock

133

114

View full text Add to dashboard Cite

show abstract

“…For example, the combination of GM-CSF, IL-4, and TNFα induced the expression of MHC II, CD40, CD86, CD1a, CD1b, and CD1c, whereas the combination of GM-CSF, TNFα and IFN-γ triggered MHC II, CD80, CD83, and CD86 expression by human neutrophils (Iking-Konert, et al, 2001; Oehler, et al, 1998). Moreover, it has been reported that neutrophils could even be reprogrammed and trans-differentiated into macrophages and DC after co-culture with multiple cytokines in vitro (Araki, et al, 2004; Iking-Konert, et al, 2005; Koffel, et al, 2014). It should be noted, however, that high (generally non-physiologic) concentrations of inflammatory factors (ranging from 1 to 100 ng/ml) were used in all these previous studies to induce the upregulation of APC markers, and differentiation could even be observed in mature end-stage neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer

et al. 2016

View full text Add to dashboard Cite

SUMMARY Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APC) in early-stage human lung cancer. These APC-like “hybrid neutrophils”, which originate from CD11b+CD15hiCD10−CD16low immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. IFN-γ and GM-CSF are requisite factors in the tumor that working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.

show abstract

“…Moreover, under inflammatory conditions, band-stage neutrophils were recently shown to transdifferentiate into monocytes [207]. Metabolic reprogramming, including the induction of anabolic pro-survival pathways, has been described in CF airway neutrophils, including up-regulation of the mammalian target of rapamycin (mTOR) pathway [208] and nutrient/glucose transporters [209].…”

Section: Neutrophil Heterogeneity and Plasticitymentioning

confidence: 99%

Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury

et al. 2015

View full text Add to dashboard Cite

Neutrophils, the most abundant human immune cells, are rapidly recruited to sites of infection, where they fulfill their life-saving antimicrobial functions. While traditionally regarded as short-lived phagocytes, recent findings on long-term survival, neutrophil extracellular trap (NET) formation, heterogeneity and plasticity, suppressive functions, and tissue injury have expanded our understanding of their diverse role in infection and inflammation. This review summarises our current understanding of neutrophils in host-pathogen interactions and disease involvement, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage.

show abstract

Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation

Abstract: Key Points Our study delineates a signaling pathway and molecular mechanism that band-stage neutrophils acquire to gain monocytic characteristics. Band-stage neutrophils from G-CSF–mobilized blood differentiate into monocytic cells upon recruitment to inflammatory sites.

Cited by 41 publications

References 64 publications

Immune Cell Phenotype and Function in Sepsis

Immune Cell Phenotype and Function in Sepsis

Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer

Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury

Contact Info

Product

Resources

About