Alkaline Serine Proteinase from Aspergillus fumigatus Has Synergistic Effects on Asp-f-2-Induced Immune Response in Mice

2002 ◽  
Vol 129 (2) ◽  
pp. 129-137 ◽  
Author(s):  
Viswanath P. Kurup ◽  
Jin-Qi Xia ◽  
Horng-Der Shen ◽  
David A. Rickaby ◽  
James D. Henderson Jr ◽  
...  
1985 ◽  
Vol 92 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Luuk A.Th. Hilgers ◽  
Harm Snippe ◽  
Margriet Jansze ◽  
Jan M.N. Willers

2010 ◽  
Vol 59 (6) ◽  
pp. 625-633 ◽  
Author(s):  
John P. Fallon ◽  
Emer P. Reeves ◽  
Kevin Kavanagh

The filamentous fungus Aspergillus fumigatus produces a variety of enzymes and toxins that may facilitate fungal colonization of tissue and evasion of the host immune response. One such toxin, fumagillin, was investigated for its ability to inhibit the action of neutrophils, which are a central component of the innate immune response to microbial infection. Neutrophils exposed to 2 μg fumagillin ml−1 for 25 min showed a significantly reduced ability to kill yeast cells (P<0.02), to phagocytose conidia of A. fumigatus (P<0.023) and to consume oxygen (P<0.032). The ability of neutrophils to generate superoxide is dependent upon the action of a functional NADPH oxidase complex which is composed of cytosolic (p40phox, p47phox, p67phox, Rac2) and membrane (gp91phox) proteins. Exposure of neutrophils to fumagillin inhibited the formation of the NADPH oxidase complex by blocking the translocation of p47phox from the cytosolic to the membrane fraction (P=0.02). In addition to the production of superoxide, neutrophils also undergo degranulation, which leads to the release of proteolytic enzymes that contribute to the microbicidal activity of the cell. Fumagillin-treated neutrophils showed reduced degranulation as evidenced by lower myeloperoxidase activity (P<0.019). Fumagillin-treated cells demonstrated reduced levels of F-actin, thus indicating that retarding the formation of F-actin may contribute to the inhibition of the structural rearrangements required in the activated neutrophil. This work indicates that fumagillin may contribute to reducing the local immune response by altering the activity of neutrophils and thus facilitate the continued persistence and growth of A. fumigatus in the host.


2015 ◽  
Vol 83 (9) ◽  
pp. 3590-3600 ◽  
Author(s):  
Mirjam Urb ◽  
Brendan D. Snarr ◽  
Gabriella Wojewodka ◽  
Mélanie Lehoux ◽  
Mark J. Lee ◽  
...  

Airway colonization by the moldAspergillus fumigatusis common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization withA. fumigatushyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established anin vivomodel to study the natural history of airway colonization with liveA. fumigatushyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4+T cells, followed by a rise in IL-17 and Foxp3+cells by day 14. These results provide the first report of the evolution of the immune response toA. fumigatushyphal colonization.


2012 ◽  
Vol 61 (6) ◽  
pp. 643-648 ◽  
Author(s):  
Zhuo-zhe Li ◽  
Li-li Tao ◽  
Jing Zhang ◽  
Hui-jun Zhang ◽  
Jie-Ming Qu

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
H. P. Huemer

A variety of drugs which are not primarily considered to be immunosuppressive agents have been described to modulate the humoral and cellular immune response in humans or animals. Thereby they may have an influence on the effectiveness and possible side effects of vaccines. This mini review lists some of the different substance classes and also some of endogeneous, infectious, nutritional, and environmental influences with suspected capability to interfere with immunizations. Studies in most cases focused on substances with known immunosuppressive functions, but there is growing evidence for immunomodulatory effects also of commonly used drugs with wide distribution. In particular combinations of those antiproliferative and antiphlogistic side effects of different substance classes have not been studied in detail but may substantially interfere with the development of a functional humoral and cellular immune response. The drugs of importance include antipyretics, anticoagulants, tranquilizers, and substances influencing lipid metabolism but also commonly used drugs of abuse like alcohol or cannabinoids. Additional substances of environmental, nutritional, or microbiological origin may also play a role but their combinatory/synergistic effects have been disregarded so far due to the lack of systematic data and the complex study designs necessary to elucidate those complex epidemiologic questions.


2006 ◽  
Vol 21 (2) ◽  
pp. 20-27 ◽  
Author(s):  
Bhanu P. Singh ◽  
Banani Banerjee ◽  
Puspanita Naik ◽  
Jordan N. Fink ◽  
Viswanath P. Kurup

1998 ◽  
Vol 24 (3) ◽  
pp. 233-251 ◽  
Author(s):  
Paolo Ladarola ◽  
Giuseppe Lungarella ◽  
Piero A. Martorana ◽  
Simona Viglio ◽  
Maria Guglielminetti ◽  
...  

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