Abstract
Pneumocystis jirovecii, the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity. The small-molecule inhibitor BRD5529 was able to significantly reduce both phospho-p38 and phospho-pERK1 signaling and tumor necrosis factor alpha (TNF-α) release during stimulation of macrophages with Pneumocystis cell wall β-glucans.
Original language | English (US) |
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Article number | e01210 |
Journal | Antimicrobial Agents and Chemotherapy |
Volume | 64 |
Issue number | 11 |
DOIs | |
State | Published - Oct 2020 |
Keywords
- CARD9
- Inflammation
- Inhibitor
- Macrophages
- Pneumocystis carinii
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases