Dermatophytes contain a novel lipid-like leukocyte activator

In the early phase of dermatophytosis, neutrophils are regularly detected microscopically in the infected skin. Although neutrophil recruitment may at least in part occur indirectly by complement activation, we asked whether dermatophytes might release chemoattractants for neutrophils. We cultivated various strains of different dermatophytes and tested fungal extracts for the presence of neutrophil chemotactic activity. As a result, we detected neutrophil chemotactic activity only in diethylether extracts, but not in aqueous extracts. We purified this lipid-like leukocyte activator (LILA) to apparent homogeneity by reversed-phase high performance liquid chromatography and found that purified LILA does not show ultraviolet absorption at wavelengths > 210 nm. Biologic studies revealed that LILA is as effective as formyl-methionyl-leucyl-phenylalanine in eliciting neutrophil chemotaxis, degranulation, and activation of the respiratory burst. Desensitization experiments in chemotaxis and degranulation with leukotriene B4, platelet-activating factor, or 5-oxo-eicosanoids revealed that LILA does not cross-desensitize with any of these other lipid-like attractants and thus possibly acts via a distinct as yet postulated neutrophil receptor. It is hypothesized that LILA, similarly to formylated methionyl peptides in bacteria, represents a dermatophyte- and possibly fungus-specific lipid compound that allows the host phagocytes to specifically recognize fungal infection. This system would be similar to the recognition of bacteria by phagocytes via N-formylated methionyl peptides, which represent a characteristic and unique system to identify bacteria.