Targeting CARD9 with Small-Molecule Therapeutics Inhibits Innate Immune Signaling and Inflammatory Response to Pneumocystis carinii ß-Glucans.
Antimicrob Agents Chemother
; 64(11)2020 10 20.
Article
in En
| MEDLINE
| ID: mdl-32839216
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 ß-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 ß-glucans.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pneumocystis
/
Pneumonia, Pneumocystis
/
Pneumocystis carinii
/
Beta-Glucans
Limits:
Humans
Language:
En
Journal:
Antimicrob Agents Chemother
Year:
2020
Type:
Article
Affiliation country:
United States