Effects of combination of Cryptococcus gattii and IFN-γ, IL-4 or IL-27 on human bronchial epithelial cells.

BACKGROUND: Airway epithelial cells are crucial for the establishment of cryptococcosis. In experimental cryptococcosis, the Th2 immune response is associated with host susceptibility, while Th1 cells are associated with protection. The absence of IL-27 receptor alpha in mice favor the increase Cryptococcus neoformans burden in the lung. Here, we evaluated the effects of the combination of IL-4, IFN-γ or IL-27 with C. gattii on human bronchial epithelial cells (BEAS-2B). METHODS: BEAS-2B were stimulated with IL-4, IFN-γ or IL-27 (100 ng/mL) and/or live yeast forms of C. gattii (multiplicities of infection (MOI) of 1-100) and vice-versa, as well as with heat-killed cells of C. gattii for 24 h. RESULTS: None of the C. gattii MOIs had cytotoxic effects on BEAS-2B when compared to control. The cells stimulated by cytokines (IL-4, IFN-γ or IL-27) followed by live yeast forms of C. gattii (MOI of 100) infection and vice-versa demonstrated a reduction in IL-6, IL-8 and/or CCL2 production and activation of STAT6 (induced by IL-4) and STAT1 (induced by IL-27 or IFN-γ) when compared to cells stimulated with C. gattii, IL-4, IFN-γ or IL-27. In the combination of cytokines and heat-killed cells of C. gattii, no inhibition of these inflammatory parameters was observed. The growth of C. gattii was increased while the phagocytosis of live yeast forms of C. gattii in the BEAS-2B were reduced in the presence of IL-4, IFN-γ or IL-27. Conclusion The association of live yeast forms, but not heat-killed yeast forms, of C. gattii with IL-4, IFN-γ or IL-27 induced an anti-inflammatory effect.

The anti-inflammatory and pro-resolution effects of aspirin-triggered RvD1 (AT-RvD1) on peripheral blood mononuclear cells from patients with severe asthma.

Asthma is an inflammatory disease that is characterized by a predominance of eosinophils and/or neutrophils in the airways. In the resolution of inflammation, lipid mediators such as resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1 (AT-RvD1) are produced and demonstrate anti-inflammatory and pro-resolution effects. In experimental models such as airway allergic inflammation induced by ovalbumin in mice, RvD1 and AT-RvD1 alleviate some of the most important phenotypes of asthma. Here, we demonstrated the effects of AT-RvD1 on peripheral blood mononuclear cells (PBMCs) from healthy individuals and patients with severe asthma stimulated with lipopolysaccharide (LPS) or Dermatophagoides pteronyssinus (DM). AT-RvD1 (100nM) reduced the concentration of TNF-α in PBMCs from healthy individuals and patients with severe asthma stimulated with LPS or DM. In addition, AT-RvD1 lowered the production of IL-10 only in PBMCs from patients with severe asthma stimulated with LPS. These effects were associated in part with decreasing NF-κB activation. Moreover, AT-RvD1 significantly increased phagocytosis of apoptotic neutrophils by monocytes from patients with severe asthma. In conclusion, AT-RvD1 demonstrated both anti-inflammatory and pro-resolution effects in PBMCs from patients with severe asthma and could become in the future an alternative treatment for asthma.