Pseudomonas aeruginosa Airway Infection Recruits and Modulates Neutrophilic Myeloid-Derived Suppressor Cells

Öz, Hasan Halit; Zhou, Benyuan; Voß, P.; Carevic, Melanie; Schroth, Carolin; Frey, Nina; Rieber, Nikolaus; Hector, Andreas; Hartl, Dominik

doi:10.3389/fcimb.2016.00167

Cited by 24 publications

(24 citation statements)

References 25 publications

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“…CFTR has been demonstrated to have a functional role in phagolysosomal activity in both macrophages 30 and neutrophils, 31 32 and the absence of CFTR promotes inflammatory cytokine release from macrophages. 14 33 CFTR has also been implicated in the regulation of T cell suppression by myeloid suppressor cells 34 and, as such, a diverse but functional role of CFTR in myeloid cells has now been established.…”

Section: Discussionmentioning

confidence: 99%

Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis

Gray

Hardisty

Regan

et al. 2017

Thorax

160

149

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BackgroundCystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation. We hypothesised that the delay in apoptosis in CF is a primary defect and preferentially allows CF neutrophils to form NETs, contributing to inflammation.MethodsBlood neutrophils were isolated from patients with CF, CF pigs and appropriate controls. Neutrophils were also obtained from patients with CF before and after commencing ivacaftor. Apoptosis was assessed by morphology and flow cytometry. NET formation was determined by fluorescent microscopy and DNA release assays. NET interaction with macrophages was examined by measuring cytokine generation with ELISA and qRT-PCR.ResultsCF neutrophils live longer due to decreased apoptosis. This was observed in both cystic fibrosis transmembrane conductance regulator (CFTR) null piglets and patients with CF, and furthermore was reversed by ivacaftor (CFTR potentiator) in patients with gating (G551D) mutations. CF neutrophils formed more NETs and this was reversed by cyclin-dependent kinase inhibitor exposure. NETs provided a proinflammatory stimulus to macrophages, which was enhanced in CF.ConclusionsCF neutrophils have a prosurvival phenotype that is associated with an absence of CFTR function and allows increased NET production, which can in turn induce inflammation. Augmenting neutrophil apoptosis in CF may allow more appropriate neutrophil disposal, decreasing NET formation and thus inflammation.

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Section: Discussionmentioning

confidence: 99%

Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis

Gray

Hardisty

Regan

et al. 2017

Thorax

160

149

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“…This Th2–Th17 axis may even dispose for acquiring P. aeruginosa lung infections, although this has not yet been fully clarified . Interestingly, recruitment of neutrophil myeloid‐derived suppressor (MDSCs) cells which can suppress T‐cell responses has recently been reported in CF . In contrast to what would be expected, presence of neutrophil MDSCs in peripheral blood correlated with improved lung function in CF .…”

Section: Biofilm Infections and Acquired Immune Responsementioning

confidence: 99%

Biofilms and host response – helpful or harmful

Moser

Pedersen

Lerche

et al. 2017

APMIS

127

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host response -helpful or harmful. APMIS 2017; 125: 320-338.Biofilm infections are one of the modern medical world's greatest challenges. Probably, all non-obligate intracellular bacteria and fungi can establish biofilms. In addition, there are numerous biofilm-related infections, both foreign bodyrelated and non-foreign body-related. Although biofilm infections can present in numerous ways, one common feature is involvement of the host response with significant impact on the course. A special characteristic is the synergy of the innate and the acquired immune responses for the induced pathology. Here, we review the impact of the host response for the course of biofilm infections, with special focus on cystic fibrosis, chronic wounds and infective endocarditis.

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“…To bypass this limitation, MDSCs isolated from sepsis mice are infused into wild-type recipient mice subjected to microbial insults. The adoptive transfer of Gr-1 + CD11b + MDSCs or PMN-MDSCs harvested from septic donor-mice into recipient mice protects the later from acute endotoxemia, rapidly lethal CLP and Pseudomonas airway infection (54, 60, 65–68). Two studies compare the benefits provided by the infusion of Gr-1 + CD11b + MDSCs taken either quickly or late after the onset of infection (i.e., 3 vs. 10–12 days post-infection).…”

Section: Mdscs Expansion and Activationmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells in Sepsis

2019

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Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells characterized by their immunosuppressive functions. MDSCs expand during chronic and acute inflammatory conditions, the best described being cancer. Recent studies uncovered an important role of MDSCs in the pathogenesis of infectious diseases along with sepsis. Here we discuss the mechanisms underlying the expansion and immunosuppressive functions of MDSCs, and the results of preclinical and clinical studies linking MDSCs to sepsis pathogenesis. Strikingly, all clinical studies to date suggest that high proportions of blood MDSCs are associated with clinical worsening, the incidence of nosocomial infections and/or mortality. Hence, MDSCs are attractive biomarkers and therapeutic targets for sepsis, especially because these cells are barely detectable in healthy subjects. Blocking MDSC-mediated immunosuppression and trafficking or depleting MDSCs might all improve sepsis outcome. While some key aspects of MDSCs biology need in depth investigations, exploring these avenues may participate to pave the way toward the implementation of personalized medicine and precision immunotherapy for patients suffering from sepsis.

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Pseudomonas aeruginosa Airway Infection Recruits and Modulates Neutrophilic Myeloid-Derived Suppressor Cells

Cited by 24 publications

References 25 publications

Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis

Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis

Biofilms and host response – helpful or harmful

Myeloid-Derived Suppressor Cells in Sepsis

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