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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

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Visualizing the Selectivity and Dynamics of Interferon Signaling In Vivo.

Sebastian A Stifter¹, Nayan Bhattacharyya¹, Andrew J Sawyer¹

¹Immunology and Host Defense Group, Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia; Centenary Institute, The University of Sydney, NSW 2050, Australia.

|December 12, 2019

Summary

This summary is machine-generated.

Interferon (IFN) signaling in vivo is complex, with responses varying by cell type and location. This study reveals how distinct IFN signals dictate cellular responses and infection susceptibility.

Keywords:

Irgm1 epithelial cells influenza interferon receptor signaling interferons lung viral infection

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Area of Science:

Immunology
Cell Biology
Virology

Background:

Interferons (IFNs) are crucial cytokines for host defense against pathogens.
The precise identity and distribution of IFN-responsive cells in vivo remain poorly understood.
Understanding IFN responses is vital for developing effective antiviral strategies.

Purpose of the Study:

To generate a reporter mouse model for all three types of IFNs.
To investigate the spatio-temporal dynamics and cellular identity of IFN-responding cells.
To explore IFN response heterogeneity in vivo during IFN injection and influenza infection.

Main Methods:

Generation of a novel mouse strain to report IFN signaling.
Intraperitoneal injection of IFNs and subsequent influenza virus infection.
Analysis of cellular responses, including signaling strength and temporal dynamics.

Main Results:

Cellular responses to IFNs in vivo are highly heterogeneous, influenced by anatomical site, cell type, IFN type preference, and activation status.
Type I and II pneumocytes, key targets of influenza, show distinct IFN signaling patterns.
Differential IFN signaling strength and dynamics correlate with varied susceptibility to influenza virus infection.

Conclusions:

IFN responses in vivo are not uniform but are finely tuned by cellular context.
The integration of distinct IFN signals over time and by cell type determines the specificity and magnitude of the immune response.
These findings provide critical insights into host-pathogen interactions and immune regulation.