Tartrate Resistant Acid Phospatase: the entangled enzyme in viral toll-like receptor signaling

Baalman, Leo (2022) Tartrate Resistant Acid Phospatase: the entangled enzyme in viral toll-like receptor signaling. Research Project, Pharmacy.

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Abstract

Acute exacerbations are impactful events characterized by a rapid decline in lung function and are mainly caused by viral infections, ultimately driving a poor outcome of COPD patients. Exacerbating patients have shown to react differently upon viral infections compared to healthy subjects, but the mechanism remains elusive. TRAP is an enzyme that is expressed in osteoblasts and alveolar macrophages. In bone, the role of TRAP is well defined but its function in the lung has yet to be determined. Therefore, we set out to establish the effect of this enzyme on anti-viral and pro-inflammatory cytokine excretion via endosomal viral toll-like receptors TLR7 and 8 by using genetic analysis and cytokine quantifying techniques. We found TLR7 signaling to be linked with ACP5 (TRAP encoding gene), and despite being species and cell-type specific, we discovered that TRAP can selectively stimulate both anti-viral and pro-inflammatory cytokine production in murine as well as human immune cells. Where and how TRAP interacts is still unknown, but it may be involved in TLR trafficking to the endosomal compartments, link with the endosomal receptor, or interact with downstream regulators in the cytoplasm. Overall, these findings clearly show a link between ACP5/TRAP and viral immunity. Therefore, determining the exact role of ACP5/TRAP in the lung could be crucial to increase viral clearance and decrease excessive inflammation in exacerbating patients.

Item Type:	Thesis (Research Project)
Supervisor name:	Melgert, B.N.
Degree programme:	Pharmacy
Thesis type:	Research Project
Language:	English
Date Deposited:	20 Sep 2022 11:56
Last Modified:	20 Sep 2022 11:56
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/28737

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