Analysis of the in vitro activity of human neutrophils against Aspergillus fumigatus in presence of antifungal and immunosuppressive agents

Decker, Christina; Wurster, Sebastian; Lazariotou, Maria; Hellmann, Anna Maria; Einsele, Hermann; Ullmann, Andrew J.; Löffler, Jürgen

doi:10.1093/mmy/myx069

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…Therefore, we assume that patients can be treated with FLC or VRC without expecting relevant immunomodulatory side effects. However, another group recently reported significantly lowered formation of NETs in the presence of VOR (49). As NETosis is dependent on NADPH-oxidase production of ROS (23), which was unaffected through VRC in our experiments, this detail might not directly result in impaired antifungal killing.…”

Section: Discussioncontrasting

confidence: 41%

“…However, synergistic effects of LAMB and PMN with regard to induction of hyphal damage as measured by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt (XTT) metabolic assay were described before (65), indicating an interplay at least in antifungal defense in addition to our in vitro findings. Of note, we also did not test PMN for NET formation despite recent reports of significantly lowered formation of NETs in the presence of LAMB or AMB (49). However, this could not be explained through lowered generation of ROS resulting in impaired NETosis, as we found increased (AMB) or rather unaffected ROS production (LAMB) in PMN after drug prestimulation.…”

Section: Discussionmentioning

confidence: 65%

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Antifungal Drugs Influence Neutrophil Effector Functions

Ries

Alflen

Lopez

et al. 2019

Antimicrob Agents Chemother

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There is a growing body of evidence for immunomodulatory side effects of antifungal agents on different immune cells, e.g., T cells. Therefore, the aim of our study was to clarify these interactions with regard to the effector functions of polymorphonuclear neutrophils (PMN). Human PMN were preincubated with fluconazole (FLC), voriconazole (VRC), posaconazole (POS), isavuconazole (ISA), caspofungin (CAS), micafungin (MFG), conventional amphotericin B (AMB), and liposomal amphotericin B (LAMB). PMN then were analyzed by flow cytometry for activation, degranulation, and phagocytosis and by dichlorofluorescein assay to detect reactive oxygen species (ROS). Additionally, interleukin-8 (IL-8) release was measured by enzyme-linked immunosorbent assay. POS led to enhanced activation, degranulation, and generation of ROS, whereas IL-8 release was reduced. In contrast, ISA-pretreated PMN showed decreased activation signaling, impaired degranulation, and lower generation of ROS. MFG caused enhanced expression of activation markers but impaired degranulation, phagocytosis, generation of ROS, and IL-8 release. CAS showed increased phagocytosis, whereas degranulation and generation of ROS were reduced. AMB led to activation of almost all effector functions besides impaired phagocytosis, whereas LAMB did not alter any effector functions. Independent from class, antifungal agents show variable influence on neutrophil effector functions in vitro. Whether this is clinically relevant needs to be clarified.

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Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 65%

Antifungal Drugs Influence Neutrophil Effector Functions

Ries

Alflen

Lopez

et al. 2019

Antimicrob Agents Chemother

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“…Interestingly, some antifungal drugs also have inhibitory effects on NETs. Traditional amphotericin B, liposomal amphotericin B, and voriconazole can inhibit the release of NETs by neutrophils co-cultured with inactivated A. fumigatus hyphae (Decker et al, 2018). The influence of this phenomenon on the effects of antifungal drugs remains to be studied.…”

Section: Netosis Provides New Ideas For Clinical Antifungal Strategiesmentioning

confidence: 99%

The emerging role of neutrophil extracellular traps in fungal infection

Liang

Lian

2022

Front. Cell. Infect. Microbiol.

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Fungal infections are global public health problems and can lead to substantial human morbidity and mortality. Current antifungal therapy is not satisfactory, especially for invasive, life-threatening fungal infections. Modulating the antifungal capacity of the host immune system is a feasible way to combat fungal infections. Neutrophils are key components of the innate immune system that resist fungal pathogens by releasing reticular extracellular structures called neutrophil extracellular traps (NETs). When compared with phagocytosis and oxidative burst, NETs show better capability in terms of trapping large pathogens, such as fungi. This review will summarize interactions between fungal pathogens and NETs. Molecular mechanisms of fungi-induced NETs formation and defensive strategies used by fungi are also discussed.

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“…Neutrophils play an essential role in counteracting mycoses, including NET release, as recently revised ( Urban and Nett, 2019 ). Both amphotericin B, usually used in severe cases ( Hamill, 2013 ), and voriconazole, a drug of choice in invasive aspergillosis ( Malani et al, 2015 ), decreased NET formation ( Decker et al, 2018 ).…”

Section: Pharmacological Modulation Of Net Formation Via Drugsmentioning

confidence: 99%

Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

et al. 2021

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Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

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Analysis of the in vitro activity of human neutrophils against Aspergillus fumigatus in presence of antifungal and immunosuppressive agents

Cited by 3 publications

References 23 publications

Antifungal Drugs Influence Neutrophil Effector Functions

Antifungal Drugs Influence Neutrophil Effector Functions

The emerging role of neutrophil extracellular traps in fungal infection

Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

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