3M-003, An Agonist Of Toll-like Receptors (TLRs) 7 And 8, Significantly Upregulates Effector Cell Anti-fungal Activity.

E. BRUMMER1, M. A. ANTONYSAMY 2, L. BYTHADKA 3, G. W. GULLIKSON 2, D. A. STEVENS 1;

Author address: 

1Sta. Clara Vly. Med. Ctr./Stanford U., San Jose, CA, 23M Pharmaceuticals, St. Paul, MN, 3Calif. Inst. Med. Res., San Jose, CA.

Abstract: 

Background. TLRs have been recently recognized as critical in natural host defense against fungal pathogens. 3M-003 (MW 318) is structurally similar to the imidazoquinolone, imiquimod. We evaluated, for the first time, the antifungal properties of 3M-003, in killing (reduction of CFU) of Candida albicans by all effector cell lineages: monocytes (Mo), neutrophils (N), macrophages (Ma). Methods. Mouse splenocytes or peripheral blood mononuclear cells (PBMC) were stimulated in vitro with 3M-003, and PBMC at 1 and 3 μM 3M-003 at 24h found to be optimal for TNFα and IL-12p40 production. Supernatants (sup) of the 24h cultures were harvested for indirect assay. Results. In testing the direct effect of drug, the positive control, IFNγ (1000 U/mL), but not 3M-003 (up to 10 μg/mL), pretreatment for 24h enhanced mouse Mo and N killing in 2-4h assays. However, 0.1-80 μg/mL 3M-003 enhanced peritoneal(P) Ma killing: control (C) 0-15%, 3M-003 21-45% (p
2006

abstract No: 

F2-1176

Full conference title: 

46th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 46th