Extracellular Paracoccidioides brasiliensis phospholipase B involvement in alveolar macrophage interaction
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2010
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Background: Phospholipase B (PLB) has been reported to be one of the virulence factors for human pathogenic
fungi and has also been described as necessary for the early events in infection. Based on these data, we
investigated the role of PLB in virulence and modulation of the alveolar pulmonary immune response during
infection using an in-vitro model of host-pathogen interaction, i.e. Paracoccidioides brasiliensis yeast cells infecting
alveolar macrophage (MH-S) cells.
Results: The effect of PLB was analyzed using the specific inhibitor alexidine dihydrochloride (0.25 μM), and
pulmonary surfactant (100 μg mL -1 ), during 6 hours of co-cultivation of P. brasiliensis and MH-S cells. Alexidine
dihydrochloride inhibited PLB activity by 66% and significantly decreased the adhesion and internalization of yeast
cells by MH-S cells. Genes involved in phagocytosis (trl2, cd14) and the inflammatory response (nfkb, tnf-a, il-1b)
were down-regulated in the presence of this PLB inhibitor. In contrast, PLB activity and internalization of yeast cells
significantly increased in the presence of pulmonary surfactant; under this condition, genes such as clec2 and the
pro-inflammatory inhibitor (nkrf) were up-regulated. Also, the pulmonary surfactant did not alter cytokine
production, while alexidine dihydrochloride decreased the levels of interleukin-10 (IL-10) and increased the levels of
IL-12 and tumor necrosis factor-a (TNF-a). In addition, gene expression analysis of plb1, sod3 and icl1 suggests that
P. brasiliensis gene re-programming is effective in facilitating adaptation to this inhospitable environment, which
mimics the lung-environment interaction.
Conclusion: P. brasiliensis PLB activity is involved in the process of adhesion and internalization of yeast cells at the
MH-S cell surface and may enhance virulence and subsequent down-regulation of macrophage activation.
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SOARES, Deyze Alencar et al. Extracellular Paracoccidioides brasiliensis phospholipase B involvement in alveolar macrophage interaction. BMC Microbiology , London, v. 10, n. 241, p. 2-9, Sept. 2010.