Human neutrophils susceptibility to Paracoccidioides brasiliensis: an ultrastructural and cytochemical assay

Abstract

Paracoccidioidomycosis, caused by the dimorphic fungus Paracoccidioides brasiliensis, is the most prevalent systemic mycosis of Latin America, with Brazil accounting for 80% of the reported cases. The great number of neutrophils found in P. brasiliensis granulomas demonstrates the importance of polymorphonuclear neutrophils (PMN) cells during this mycotic infection. It has been found that neutrophils from healthy human donors can ingest and kill the fungus through a typical phagocytic process. The present work tests the phagocytic ability of neutrophils collected from patients that had had and were considered cured of paracoccidioidomycosis. Transmission electron microscopy and cytochemical studies indicate that patients' neutrophils eventually degenerate during phagocytosis of P. brasiliensis. Endogen peroxidase and NAD(P)H-oxidase are activated during the process showing that the respiratory burst and the neutrophil degranulation are triggered by the attachment of the yeast cells. Apparently these processes are not enough to kill P. brasiliensis. Although fungicidal activity can be determined by colony forming unit (CFU) counting, qualitative data suggest, as noted, that neutrophils from patients with treated paracoccidioidomycosis degenerate during the phagocytosis process. Hence, this work demonstrates the existence of a functional neutrophil deficiency against P. brasiliensis in susceptible individuals. The exact origin of this susceptibility is still to be determined in further studies.