Interferon-gamma enhances phagocytosis, the production of reactive oxygen species and pro-inflammatory cytokines – implications for innate and acquired immunity.

Abstract

Neutrophils and interferon-γ (IFN-γ) are known critical components of innate and acquired immune responses.However, recent studies have demonstrated that these two immune functions are not entirely isolated. Treatment of neutrophils with IFN-γ elicits a variety of responses depending on the stimulus and on environmental conditions. In view of the physiological and pathophysiological importance of the regulatory activity of IFN-γ in neutrophil functions and the diverse, sometimes conflicting results reported, we decided to investigate the effects of this cytokine on phagocytosis, the production of reactive oxygen species (ROS) and the release of lysosome enzymes, as mediated by different types of immune receptors in mouse neutrophils. We found increased phagocytic capacity of mouse neutrophils, which was accompanied by the up-regulation of FcγR, CR, and the dectin-1 receptor. The increase in ROS production mediated by these receptors with the activation of NADPH oxidase is correlated with the increased expression of p47 phox and gp91 phox mRNA. In addition to enhanced phagocytosis, we also observed the release of some lysosomal enzymes. The increased production of reactive oxygen species may be important for the enhanced capacity for killing phagocytosed microorganisms but may also favor the induction of oxidative stress in adjacent cells. In agreement with this potential inflammatory role, we also demonstrated the increased release of the inflammatory cytokines TNF-α and IL-6 from neutrophils treated with recombinant IFN-γ. These results show that IFN-γ can act as a signaling molecule for neutrophils, modulating their functions in innate as well as acquired immunity. This Research Highlight discusses the findings of our recent study and active research endeavors.

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“…The precise role of IFN-γ in health is complex, since it has an important role in the control of inflammation, ranging from the migration of leukocytes to the activation of its effector function (Rauch et al, 2013). It also stimulates the production of reactive oxygen species and inflammatory cytokines (Marchi, 2014). A recent study showed an association between reduced IFN-γ and increased HDL-cholesterol levels in elderly women enrolled in an exercise program (Nishida et al, 2015), which pointed to the beneficial effect of physical training on lipid profile associated with the reduction of circulating IFN-γ.…”