Search results for "Aspergillus fumigatus"

2019

s2 integrin receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit, and are differentially expressed by leukocytes. s2 integrins are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Functional loss of CD18-termed leukocyte-adhesion deficiency type 1 (LAD1)-results in an immunocompromised state characterized by frequent occurrence of severe infections. In immunosuppressed individuals Aspergillus fumigatus is a frequent cause of invasive pulmonary fungal infection, and often occurs in patients suffering from LAD1. Here, we asked for the importance of CD11b/CD18 also termed MAC-1 which …

Neutrophil extracellular traps impair fungal clearance in a mouse model of invasive pulmonary aspergillosis

2019

Abstract Neutrophil extracellular traps (NETs) are formed by polymorphonuclear neutrophils (PMN) and contribute to the innate host defense by binding and killing bacterial and fungal pathogens. Because NET formation depends on histone hypercitrullination by peptidylarginine deiminase 4 (PAD4), we used PAD4 gene deficient (Pad4-/-) mice in a mouse model of invasive pulmonary aspergillosis (IPA) to address the contribution of NETs to the innate host defense in vivo. After the induction (24 h) of IPA by i.t. infection with Aspergillus fumigatus conidia, Pad4-/- mice revealed lower fungal burden in the lungs, accompanied by less acute lung injury, TNFα and citH3 compared to wildtype controls. T…

Nanoparticle decoration impacts airborne fungal pathobiology

2018

Airborne fungal pathogens, predominantly Aspergillus fumigatus, can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization. Nanoparticle-spore complex formation was enhanced by small nanoparticle size rather than by material, charge, or "stealth" modifications and was concentration-dependently reduced by the formation of environmental or physiological biomolecule coronas. Assembly of nanoparticle-spore surface hybrid s…

Neutrophil Recruitment Is Regulated By Adamts-13 in a Murine Model of Invasive Aspergillosis

2015

Abstract Introduction: During inflammation von Willebrand factor (VWF) multimers are secreted as an acute phase protein whereupon the size and the prothrombotic activity play an essential role. The size of VWF multimers is regulated by the specific proteolytic activity of ADAMTS-13 (a disintegrin and metalloprotease with ThromboSpondin type 1 repeats-13) which is diminished under several pathological conditions. Employing a murine model of invasive pulmonary aspergillosis (IPA) we aimed to determine the relevance of this regulatory pathway for innate inflammatory responses and polymorphonuclear neutrophil (PMN) recruitment which is crucial for fungal clearance and survival. Methods: IPA was…

Multiple renal aspergillus abscesses in an AIDS patient: contrast-enhanced helical CT and MRI findings.

1999

Renal insufficiency or allergic reactions for X-ray contrast agents are frequent limitations in immunocompromised hosts such as neutropenic or AIDS patients. Due to a better tolerance of contrast agents in MRI, this technique is well suited for investigation of parenchymal organs. We demonstrate an allergic AIDS patient who presented with fever and flank pain. At sonography, anechoic renal lesions were supposed to be non-complicated cysts; however, on T2-weighted MRI, the center was of high signal. Dynamic contrast-enhanced MRI of the kidneys demonstrated an enhancing rim with ill-defined margins. The lesions were supposed to be multiple bilateral abscesses. Due to the multiple dynamic cont…

Synthesis and biological evaluation of abietic acid derivatives

2009

A series of C18-oxygenated derivatives of abietic acid were synthesized and evaluated for their cytotoxic, antimycotic, and antiviral activities. In general, the introduction of an aldehyde group at C18 did improve the resultant bioactivity, while the presence of an acid or alcohol led to less active compounds.

Accumulation of Amphotericin B in Human Macrophages Enhances Activity against Aspergillus fumigatus Conidia: Quantification of Conidial Kill at the S…

1998

ABSTRACT A cytofluorometric assay that allowed assessment of damage to phagocytosed Aspergillus fumigatus conidia at the single-cell level was developed. After ingestion by monocyte-derived macrophages (MDMs), conidia were reisolated by treatment of the cells with streptolysin O, a pore-forming toxin with lytic properties on mammalian cells but not on fungi. The counts obtained by staining of damaged conidia with propidium iodide and quantification by cytofluorometry correlated with colony counts. By the use of this method, we demonstrate that MDMs differentiated in vitro by low-dose granulocyte-macrophage colony-stimulating factor and gamma interferon have only a limited capacity to damage…

Oxidative burst and neutrophil elastase contribute to clearance of Aspergillus fumigatus pneumonia in mice.

2014

Polymorphonuclear neutrophils (PMN) are important for the control of invasive aspergillosis (IA), a major threat to immunocompromised individuals. For clearance of Aspergillus fumigatus infections, PMN employ their potent oxidative and non-oxidative mechanisms. To clarify the relative contribution of these mechanisms, we analyzed p47(phox-/-), gp91(phox-/-) and elastase (ELA) deficient mice (ELANE) after intratracheal infection with A. fumigatus. Infected p47(phox-/-) and gp91(phox-/-) mice died within 4 days and had a significant higher fungal burden in the lungs compared to wild-type controls. Interestingly, the survival of ELANE mice after infection was unimpaired suggesting that ELA is …

Cell wall protein and glycoprotein constituents of Aspergillus fumigatus that bind to polystyrene may be responsible for the cell surface hydrophobic…

1996

Cell surface hydrophobicity (CSH) of Aspergillus fumigatus grown both in complex medium (yeast extract/peptone/dextrose; YPD) and minimal (Vogel's N) medium was monitored by assessing attachment of polystyrene microspheres to the cell surface. It was found that mature mycelium was hydrophobic. Treatment of intact mycelium with beta-mercaptoethanol (beta ME) abolished binding of the microspheres to hyphal elements, and coating of the microspheres with beta ME extracts from mycelium inhibited their attachment to intact mycelial cells. A. fumigatus mycelium was tagged in vivo with biotin and treated with beta ME. The beta ME extracts were analysed by SDS-PAGE and Western blotting with both per…

Granulocyte functions are independent of arginine availability.

2014

Abstract Arginine depletion via myeloid cell arginase is critically involved in suppression of the adaptive immune system during cancer or chronic inflammation. On the other hand, arginine depletion is being developed as a novel anti-tumor metabolic strategy to deprive arginine-auxotrophic cancer cells of this amino acid. In human immune cells, arginase is mainly expressed constitutively in PMNs. We therefore purified human primary PMNs from healthy donors and analyzed PMN function as the main innate effector cell and arginase producer in the context of arginine deficiency. We demonstrate that human PMN viability, activation-induced IL-8 synthesis, chemotaxis, phagocytosis, generation of RO…