In vitro effects of IFN-γ, IL-4 and IL-27 on human bronchial epithelial cells infected with Cryptococcus neoformans sensu stricto

Abstract

Background

The innate immune response and cytokine milieu in airway mucosa, mediated by bronchial epithelial cells, are critical in determining susceptibility or protection against cryptococcosis. In experimental models, Th2 and Th1 responses are linked to susceptibility and protection, respectively, while the roles of other cytokines remain less understood.

Aims

To evaluate the in vitro effects of IL-4, IFN-γ, and IL-27 (100 ng/mL) on human bronchial epithelial cells (BEAS-2B) infected with a strain of Cryptococcus neoformans sensu stricto (multiplicities of infection [MOI] 1–100).

Methods

Cells were stimulated with each cytokine, followed by C. neoformans infection (MOI 100). After 24 h, supernatants were collected to measure CCL2, IL-6, and IL-8 production. STAT1 and STAT6 activation was analyzed by flow cytometry. Phagocytosis and colony-forming unit assays assessed fungal internalization and growth.

Results

Cytokine-stimulated, infected cells displayed reduced IL-6 and/or CCL2 production and decreased STAT6 activation (IL-4) or STAT1 activation (IL-27, IFN-γ) compared with cells stimulated with C. neoformans sensu stricto or cytokines alone. IL-27 reduced fungal internalization, while IL-4 and IFN-γ increased it. All cytokines promoted higher fungal growth.

Conclusions

The interaction of bronchial epithelial cells stimulated with IL-4, IFN-γ, or IL-27, with yeasts of C. neoformans induced an anti-inflammatory profile in the cells that impaired STAT activation and favored fungal proliferation. These findings suggest that certain cytokine environments within the airway epithelium may create conditions conducive to C. neoformans persistence, potentially influencing the progression of the infection.