Interactions of F1 fractions from different strains of Paracoccidioides brasiliensis with human complement and with human neutrophils.

Abstract

The aim of our study was to investigate differences that might exist in the activation of the human complement system by F1 fractions from four different isolates of P. brasiliensis. Isolates HC and 18 (virulent), 265 (low virulence), and 9 (intermediate virulence, attenuated) were used; before the experiments, the virulence of isolates HC and 18 was recovered by in vivo passage in guinea pigs. The four isolates of the fungus were processed for purification of F1 fractions and the activation of the human complement system was studied by a kinetic method of hemolytic activity measurement. The incubation of F1 fractions in normal human serum resulted in different degrees of inhibition of the classical and alternative pathways. The F1 fraction from the low virulence isolate was more efficient than the F1 fraction from the virulent isolates (HC and 18). Previous absorption of sera with F1 fractions completely abolished classical pathway activation. Using zymosan, instead of F1, in the absorption process caused the same phenomenon, suggesting that natural or nonspecific antibodies are responsible for the classical pathway activation. The alternative pathway activation did not depend on these antibodies, but was enhanced by their presence. On the other hand, F1 fractions from virulent isolates were more active in the stimulation of neutrophil chemiluminescence compared with the F1 fraction from the low virulence isolate. Whole P. brasiliensis yeast cells (WYC) from two distinct strains, 18 and 265, showed the same patterns of response of those observed with the F1 fractions in the functions tested. These differences in the behavior of the F1 fractions as well as WYC in relation to human complement activation and consequently to neutrophil stimulation may correlate with the virulence of individual isolates and may contribute to the understanding of the inflammatory response generation and maintenance processes in paracoccidioidomycosis.