The primary clinical limitation of the broad-spectrum antifungal compound, amphotericin B (AmB), is its significant toxicity. Hence AmB is no longer the first line of defense against many deep-seated
fungal infections, though it is inexpensive and efficacious. We hypothesized that AmB utilizes receptors highly represented in the innate immune cell repertoire, specifically
Toll-like receptors (TLR) and the cluster of differentiation-14
antigen (CD14) co-receptor, to elicit toxic effects. We based this hypothesis principally on 3 underlying facts: (1) AmB's toxic effects are inflammatory in nature, (2) AmB is a product of the Gram-positive bacterium, Streptomyces nodosus, and (3) TLR are…
