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Aspergillus Fumigatus Antigens Induce Distinct Antibody and Chemokine Responses in Human B Lymphocytes Using mTOR Dependent and Independent Pathways
Description
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A4705 - Aspergillus Fumigatus Antigens Induce Distinct Antibody and Chemokine Responses in Human B Lymphocytes Using mTOR Dependent and Independent Pathways
Author Block: M. Ali1, H. Dasari2, E. M. Carmona3; 1Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN, United States, 2Thoracic Diseases Research Unit, Mayo Clinic, Rochester, MN, United States, 3Mayo Clinic, Rochester, MN, United States.
Introduction
Aspergillus fumigatus is an airborne mold that causes various pulmonary diseases in the susceptible individuals. Recognition of distinct Aspergillus fumigatus antigens through multiple pattern-recognition receptors is central to the function of immune cells and triggers effector responses such as the release of chemokines and immunoglobulins. The aim of this study was to elucidate the immune response of B-lymphocytes to A. fumigatus. Herein, we examined the molecular mechanisms triggered by A. fumigatus β-glucans, carbohydrates found in the cell wall of the fungi (AF-G) and CpG-rich oligodeoxynucleotides (AF-ODNs) containing sequences, found in A. fumigatus genome.
Methods
B-lymphocytes isolated from peripheral blood from healthy blood donors were stimulated with AF-G and AF-ODNs. The production of cytokines and immunoglobulins were measured by qPCR and ELISA. Signaling pathways were elucidated by Immunoblotting using specific anti-phosphoprotein antibodies.
Results
Our results showed that A. fumigatus antigens stimulated the production of CCL20 and IgM. Interestingly, b-glucans stimulated B-lymphocytes to secrete CCL20, while Asp-ODN activated B cells to secrete IgM. We have previously reported that fungal β-glucans stimulate B-lymphocytes through Dectin-1 and SYK activation, whereas bacterial-ODNs stimulated B-lymphocytes via TLR9/MyD88 pathway and the mammalian target of Rapamycin (mTOR). Herein, we showed that Asp-ODN resulted in the phosphorylation/activation of the mTOR pathway via TLR9 while Asp-G was mTOR-independent but required Dectin-1 consistent with our prior observations. Furthermore, IgM secretion was abrogated in the presence of rapamycin (a well-known mTOR inhibitor) suggesting their role in IgM regulation.
Conclusion
In conclusion, this study describes a differential response of human B-lymphocytes to distinct A. fumigatus antigens and identifies the mTOR pathway in human circulating B-lymphocytes as possible modulator of the adaptive immune response to Aspergillus fumigatus.
Author Block: M. Ali1, H. Dasari2, E. M. Carmona3; 1Thoracic Disease Research Unit, Mayo Clinic, Rochester, MN, United States, 2Thoracic Diseases Research Unit, Mayo Clinic, Rochester, MN, United States, 3Mayo Clinic, Rochester, MN, United States.
Introduction
Aspergillus fumigatus is an airborne mold that causes various pulmonary diseases in the susceptible individuals. Recognition of distinct Aspergillus fumigatus antigens through multiple pattern-recognition receptors is central to the function of immune cells and triggers effector responses such as the release of chemokines and immunoglobulins. The aim of this study was to elucidate the immune response of B-lymphocytes to A. fumigatus. Herein, we examined the molecular mechanisms triggered by A. fumigatus β-glucans, carbohydrates found in the cell wall of the fungi (AF-G) and CpG-rich oligodeoxynucleotides (AF-ODNs) containing sequences, found in A. fumigatus genome.
Methods
B-lymphocytes isolated from peripheral blood from healthy blood donors were stimulated with AF-G and AF-ODNs. The production of cytokines and immunoglobulins were measured by qPCR and ELISA. Signaling pathways were elucidated by Immunoblotting using specific anti-phosphoprotein antibodies.
Results
Our results showed that A. fumigatus antigens stimulated the production of CCL20 and IgM. Interestingly, b-glucans stimulated B-lymphocytes to secrete CCL20, while Asp-ODN activated B cells to secrete IgM. We have previously reported that fungal β-glucans stimulate B-lymphocytes through Dectin-1 and SYK activation, whereas bacterial-ODNs stimulated B-lymphocytes via TLR9/MyD88 pathway and the mammalian target of Rapamycin (mTOR). Herein, we showed that Asp-ODN resulted in the phosphorylation/activation of the mTOR pathway via TLR9 while Asp-G was mTOR-independent but required Dectin-1 consistent with our prior observations. Furthermore, IgM secretion was abrogated in the presence of rapamycin (a well-known mTOR inhibitor) suggesting their role in IgM regulation.
Conclusion
In conclusion, this study describes a differential response of human B-lymphocytes to distinct A. fumigatus antigens and identifies the mTOR pathway in human circulating B-lymphocytes as possible modulator of the adaptive immune response to Aspergillus fumigatus.
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