The Role of Laccase Enzymes of Penicillium marneffei on Cytokine Production in Macrophage

Abstract

Penicillium marneffei has emerged as an opportunistic dimorphic fungus associated with Human Immunodeficiency Virus (HIV), particularly in the geographical area of endemicity in Southeast Asia and southern China. Upon host infection, one of the most important aspects that contributes to the disease outcome is the initial interaction of the P. marneffei conidia with the phagocytic cells and the induction of the inflammatory process. Laccase enzyme has been found to associate with virulence in several pathogenic fungi. To obtain a better understanding of a role of laccase in P. marneffei, conidia of laccase mutant strains or wild-type were co-cultured with THP-1, human monocyte leukemia cell line in different incubation time. The percentage of phagocytosis and phagocytic index of quadruple lac gene deletion strain were significantly higher than the wild-type at 1 and 2 hours of incubation. In addition, the significantly higher percentage of intracellular killing of the quadruple lac gene deletion strain was observed when compared with wild-type at 4 and 8 hours of incubation. The pro-inflammatory cytokines, TNF-α, IL-1β and IL-6, secreted from THP-1 infected with the quadruple lac gene deletion strain were significantly increased in comparing with the wild-type. Altogether, these results defined the role of laccase that promoted P. marneffei resistance to innate host defenses.