Patterns of Interferon Regulatory Factor 1 (IRF1) Expression By Respiratory Epithelial Cells Reveal Non-Redundancy of Type I Versus Type III Interferons

Abstract

Types I and III interferon (IFN) are co-expressed by respiratory epithelial cells (REC) in response to viral infection, and stimulate neighboring REC to express a set of interferon stimulated genes (ISG) through shared signaling pathways. Whether types I and III IFN have non-redundant functions in anti-viral defense is unknown. Because transcription factors dictate cellular phenotype and function, we hypothesized that ISG that are transcription factors (TF-ISG) mediate non-redundant functions of types I or III IFN. We treated BEAS-2B human REC with increasing doses of IFN-beta or IFN-lambda1 alone or together, and measured expression of TF-ISG and a set of “canonical” ISG by qRT-PCR and western blot. Alone, IFN-beta and IFN-lambda each induced expression of the canonical ISG and a subset of TF-ISG. By contrast, while IFN-beta alone induced IRF1 expression, it was poorly induced by IFN-lambda1 alone. Saturating doses of the two IFNs together did not enhance peak ISG transcript expression greater than either alone. Western blots revealed that while IFN-beta alone induced early and transient IRF1 expression, it was lower but sustained (through 24h) after IFN-lambda1 alone. In contrast to transcripts, saturating doses of the two IFNs together enhanced expression of IRF1 protein at 2h, 4h, and 24h greater than either of them alone. In REC, IRF1 is expressed early and relatively selectively in response to IFN-beta alone, and protein expression was enhanced after treatment with both IFNs together. IRF1 may mediate non-redundant qualitative functional responses of REC to types I and III IFN.