Exploring the protective role of recombinant type iii interferons in respiratory infections: Insights from an Mx1-deficient mouse model

Abstract

Background

Type III interferons (IFNs) are regarded as safe and effective preventive agents for viral infections of the respiratory tract. The effectiveness of the preventive use of type III IFNs in patients with polymorphisms in critical antiviral ISGs is particularly relevant. We utilized Balb/c mice deficient in the Mx1 gene as model organisms.

Methods

Recombinant IFNs were administered intranasally one day before infection with the mouse-adapted pandemic strain of influenza A virus (IAV), A/California/07/09 (H1N1pdm09). In the model of mixed infection (sequential infection with IAV at a sublethal dose and Staphylococcus aureus), a bacterial suspension was administered intranasally a day after IAV infection. Influenza nucleoprotein level and bacterial load were assessed in the lungs on the third day post-infection.

Results

Type III IFNs demonstrated a protective effect against infection with IAV. 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, 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.

Conclusion

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.