scholarly journals Immune response to n-terminal and c-terminal deletion mutants of Aspergillus fumigatus major allergen ASP F 3

2006 ◽  
Vol 21 (2) ◽  
pp. 20-27 ◽  
Author(s):  
Bhanu P. Singh ◽  
Banani Banerjee ◽  
Puspanita Naik ◽  
Jordan N. Fink ◽  
Viswanath P. Kurup
Keyword(s):  
Immune Response ◽  
Aspergillus Fumigatus ◽  
Major Allergen ◽  
Terminal Deletion ◽  
Deletion Mutants

scholarly journals Multiple signaling pathways induced by granulocyte colony-stimulating factor involving activation of JAKs, STAT5, and/or STAT3 are required for regulation of three distinct classes of immediate early genes

Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4435-4444 ◽  
Author(s):  
SS Tian ◽  
P Tapley ◽  
C Sincich ◽  
RB Stein ◽  
J Rosen ◽  
...  
Keyword(s):  
Immediate Early Genes ◽  
Signaling Molecules ◽  
Immediate Early ◽  
Terminal Deletion ◽  
Deletion Mutants ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Multiple Signaling ◽  
Stimulating Factor ◽  
Dependent Pathway

Granulocyte colony-stimulating factor (G-CSF) is the major regulator of proliferation and differentiation of neutrophilic granulocyte precursor cells. G-CSF activates multiple signaling molecules, including the JAK1 and JAK2 kinases and the STAT transcription factors. To investigate G-CSF signaling events regulated by the JAK-STAT pathway, we have generated UT7-epo cells stably expressing either wild-type (wt) G-CSF receptor or a series of C-terminal deletion mutants. Gel mobility shift and immunoprecipitation/Western analysis showed that STAT5 is rapidly activated by G-CSF in cells expressing the wt G-CSF receptor, in addition to the previously reported STAT3 and STAT1. Mutants lacking any tyrosine residues in the cytoplasmic domain maintain their ability to activate STAT5 and STAT1 but cannot activate STAT3, implying that STAT5 and STAT1 activation does not require receptor tyrosine phosphorylation. We also observed significant changes in the ratio of STAT1:STAT3:STAT5 activated by various G-CSF receptor C-terminal deletion mutants. These mutant receptors were further used to investigate the role of JAKs and STATs in G-CSF-mediated responses in these cells. We found that JAK activation correlates with G-CSF-induced cell proliferation, whereas STAT activation is not required. We have also identified three classes of G-CSF immediate early genes, whose activation correlates with the activation of distinct JAK-STAT pathways. Our data show that, whereas c-fos is regulated through a pathway independent of STAT activation, oncostatin M, IRF-1, and egr-1 are regulated by an STAT5-dependent pathway and fibrinogen is regulated by an STAT3-dependent pathway. In conclusion, our results suggest that G-CSF regulates its complex biologic activities by selectively activating distinct early response genes through different JAK-STAT signaling molecules.

C-terminal deletion mutants of the FokI restriction endonuclease

Gene ◽  
1993 ◽  
Vol 133 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Lin Li ◽  
Louisa P. Wu ◽  
Robert Clarke ◽  
Srinivasan Chandrasegaran
Keyword(s):  
Restriction Endonuclease ◽  
Terminal Deletion ◽  
Deletion Mutants

scholarly journals Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin

2010 ◽  
Vol 59 (6) ◽  
pp. 625-633 ◽  
Author(s):  
John P. Fallon ◽  
Emer P. Reeves ◽  
Kevin Kavanagh
Keyword(s):  
Immune Response ◽  
Nadph Oxidase ◽  
Aspergillus Fumigatus ◽  
Proteolytic Enzymes ◽  
Yeast Cells ◽  
Fungal Colonization ◽  
Central Component ◽  
Myeloperoxidase Activity ◽  
Microbial Infection ◽  
Nadph Oxidase Complex

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.

scholarly journals Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae

2015 ◽  
Vol 83 (9) ◽  
pp. 3590-3600 ◽  
Author(s):  
Mirjam Urb ◽  
Brendan D. Snarr ◽  
Gabriella Wojewodka ◽  
Mélanie Lehoux ◽  
Mark J. Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
Aspergillus Fumigatus ◽  
Histopathological Examination ◽  
Cell Subset ◽  
Interleukin 4 ◽  
Content Type ◽  
Cytokine Analysis ◽  
Airway Colonization ◽  
Chronic Airway

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.

scholarly journals Use of a Synthetic Peptide Epitope of Asp f 1, a Major Allergen or Antigen of Aspergillus fumigatus, for Improved Immunodiagnosis of Allergic Bronchopulmonary Aspergillosis

2004 ◽  
Vol 11 (3) ◽  
pp. 552-558 ◽  
Author(s):  
Taruna Madan ◽  
Priyanka Priyadarsiny ◽  
Mudit Vaid ◽  
Neel Kamal ◽  
Ashok Shah ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Synthetic Peptide ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Major Allergen ◽  
Specific Ige ◽  
Diagnostic Efficiency ◽  
Intradermal Testing ◽  
Peptide Epitope ◽  
Asp F 1

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is an immunologically complex allergic disorder caused by the fungal pathogen Aspergillus fumigatus. Elevated levels of total immunoglobulin E (IgE), specific IgE, and IgG antibodies in sera are important immunodiagnostic criteria for ABPA. International reference standards or standardized immunodiagnostic assays are not available due to a lack of well-defined diagnostic antigens. The present study was carried out to identify and evaluate the immunodiagnostic relevance of synthetic epitopic peptides of Asp f 1, a major allergen, antigen, or cytotoxin of A. fumigatus. Five overlapping peptides were synthesized from the N terminus of Asp f 1, one of the potential immunodominant regions predicted by algorithmic programs. The 11-amino-acid synthetic peptide (P1) significantly inhibited both IgG binding (89.10% ± 4.45%) and IgE binding (77.32% ± 3.38%) of the standardized diagnostic antigen (SDA) (a well-defined pool of diagnostically relevant allergens and antigens of A. fumigatus). With a panel of sera of ABPA patients, allergic patients with skin test negativity to A. fumigatus, and healthy individuals, P1 showed a higher diagnostic efficiency than SDA (specific IgG, 100%; specific IgE, 98.3%). The diagnostic efficiency of P1 could be attributed to the presence of homologous epitopes in various immunodominant allergens or antigens of A. fumigatus. The ability of P1 to induce histamine release from sensitized mast cells and a Th2 type of cytokine profile in peripheral blood mononuclear cells of ABPA patients suggests its potential for use in intradermal testing. P1 could be further explored for development of a standardized, specific, and sensitive immunodiagnostic test for aspergillosis.

Sign in / Sign up

Export Citation Format

Share Document