Exploring the Protective Role of Recombinant Type III Interferons in Respiratory Infections: Insights from an Mx1-Deficient Mouse Model.

Abstract

Type III interferons (IFNs) are regarded as safe and effective preventive agents for viral infections of the respiratory tract. The antiviral effects of type I and III IFNs are mediated through the induction of interferon-stimulated genes (ISGs), the variability of which influences the course of the disease and an individual's susceptibility to viruses. The effectiveness of the preventive use of type III IFNs in patients with polymorphisms in critical antiviral ISGs is particularly relevant. In this study, we utilized Balb/c mice deficient in the Mx1 gene as model organisms. Type III IFNs demonstrated a protective effect against infection with the mouse-adapted pandemic strain of influenza A virus (IAV), A/California/07/09 (H1N1pdm09). A single intranasal administration of IFN-λ protected mice from weight loss, reduced the level of viral nucleoprotein in lung homogenates, and significant differences in survival curves were also observed. In the case of mixed infection (sequential infection with IAV at a sublethal dose and Staphylococcus aureus), a single intranasal administration of IFN-λ was associated with a decrease in bacterial load in the lungs, and minimal weight loss was observed in the mice. Thus, the study demonstrated that IFN-λ can have a protective effect in Mx1-deficient Balb/c mice. These data support the universality of type III IFN use, suggesting that these preventive agents can be effective even in patients with a suboptimal genetic background.