aspergillus,gliotoxin

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Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human

neutrophils: implications for the pathogenesis of invasive aspergillosis.

[My paper] Enrico Orciuolo, Marta Stanzani, a Canestraro, Sara Galimberti,

Giovanni Carulli, , Petrini, Krishna V Komanduri

Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of

invasive aspergillosis (IA) in immunocompromised patients. In stem cell

transplant recipients, IA now occurs most frequently in the setting of therapy

with corticosteroids, including methylprednisolone (MP). We showed previously

that gliotoxin (GT), an AF-derived mycotoxin, induces apoptosis in monocytes and

dendritic cells, resulting in the suppression of AF-specific T cell responses.

We examined the ability of GT to induce apoptosis in polymorphonuclear

leukocytes (PMN) and assessed GT effects on important neutrophil functions,

including phagocytic function, degranulation, myeloperoxidase activity, and the

production of reactive oxygen species (ROS). In contrast to its effects on

monocytes, PMN remained resistant to GT-mediated apoptosis. Although many

essential neutrophil functions were unaffected, GT inhibited phagocytosis and

also induced a decrease in ROS generation by PMN. In contrast, MP therapy

potentiated ROS production, suggesting a mechanism that may facilitate tissue

injury in IA. Distinct from its effects on untreated PMN, GT augmented ROS

production in MP-treated PMN. Our results suggest that although GT may suppress

the adaptive immune response, GT may also serve to increase PMN-mediated

inflammation, which is likely to play an important role in tissue destruction in

the setting of IA.

http://lib.bioinfo.pl/pmid:17626149

Aspergillus fumigatus inhibits angiogenesis through the production of gliotoxin

and other secondary metabolites.

[My paper] Ronen Ben-Ami, E , Konstantinos Leventakos, Dimitrios P

Kontoyiannis

Department of Infectious Diseases, Infection Control and Employee Health, The

University of Texas M. D. Cancer Center, Houston, Texas, United States;

In susceptible hosts, angioinvasion by Aspergillus fumigatus triggers

thrombosis, hypoxia and proinflammatory cytokine release, all of which are

stimuli for angiogenesis. We sought to determine whether A. fumigatus directly

modulates angiogenesis. A. fumigatus culture filtrates profoundly inhibited the

differentiation, migration and capillary tube formation of human umbilical vein

endothelial cells in vitro. To measure angiogenesis at the site of infection, we

devised an in vivo matrigel assay in cyclophosphamide-treated Balb/c mice with

cutaneous invasive aspergillosis. Angiogenesis was significantly suppressed in

matrigel plugs implanted in A. fumigatus-infected mice compared with plugs from

uninfected control mice. The antiangiogenic effect of A. fumigatus was

completely abolished by deletion of the global regulator of secondary

metabolism, laeA, and to a lesser extent by deletion of gliP, which controls

gliotoxin production. Moreover, pure gliotoxin potently inhibited angiogenesis

in vitro in a dose-dependent manner. Finally, overexpression of multiple

angiogenesis-mediator encoding genes was observed in the lungs of

cortisone-treated mice during early invasive aspergillosis, whereas

gene-expression returned rapidly to baseline levels in

cyclophosphamide/cortisone-treated mice. Taken together, these results indicate

that suppression of angiogenesis by A. fumigatus both in vitro and in a

neutropenic mouse model is mediated through secondary metabolite production

http://lib.bioinfo.pl/pmid:19843884

Healthy Human T-Cell Responses to Aspergillus fumigatus Antigens.

http://lib.bioinfo.pl/pmid:20174463

Cell Microbiol. 2010 Aug 12;: 20716206 Aspergillus fumigatus: Contours of

an Opportunistic Human Pathogen.

[My paper] McCormick, Jürgen Loeffler, Ebel

Max-von-Pettenkofer-Institut, Ludwig-Maximilians-Universität, Munich, Germany.

Summary Aspergillus fumigatus is currently the major air-borne fungal pathogen.

It is able to cause several forms of disease in humans of which invasive

aspergillosis is the most severe. The high mortality rate of this disease

prompts increased efforts to disclose the basic principles of A. fumigatus

pathogenicity. According to our current knowledge, A. fumigatus lacks

sophisticated virulence traits; it is nevertheless able to establish infection

due to its robustness and ability to adapt to a wide range of environmental

conditions. This review focuses on two crucial aspects of invasive

aspergillosis:(1) properties of A. fumigatus that are relevant during infection

and may distinguish it from non-pathogenic Aspergillus species and (2)

interactions of the pathogen with the innate and adaptive immune systems.

http://lib.bioinfo.pl/pmid:20716206