Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Abstract

Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18

Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation

“…Yasui et al demonstrated that LGCs produce decreased levels of superoxide anions, which may enable M. tuberculosis to survive within granulomas ( Yasui et al, 2011 ). On the other hand, LGCs may have better fungicidal capacities than macrophages (do Nascimento et al, 2011 ; Enelow et al, 1992 ). Enelow et al demonstrated that LGCs stimulated with phorbol myristate acetate, display enhanced fungicidal capacities against C. albicans due to elevated oxidative activity ( Enelow et al, 1992 ).…”

Paracoccidioidomycosis Protective Immunity

“…The role of GM-CSF, IFN-γ, TNF-α, IL-10 and TGF-β in the generation of multinucleated giant cells, that are characteristically present in granulomas was studied, stimulating human monocytes with Paracoccidioides antigen in an in vitro setting. The authors reported that foreign body-type giant cells were preferentially induced over Langhans-type and detected an important role for GM-CSF in such giant cell formation and enhancement of fungicidal activity [132].…”