ABSTRACT
PU.1, CEBPA, and CEBPB are Lineage Determining Transcription Factors (LDTFs) that play roles in biological processes such as cell differentiation and the immune system regulation including the innate immune pathways. The roles of these LDTFs in the innate RNA and DNA sensing pathways have received little attention. We show that in buffalo fibroblasts, PU.1 causes the mRNA up-regulation of the RNA and DNA sensors such as RIG-I (65.1 fold), MDA5 (20.4 fold), IFI16-l (8.0 fold), and cGAS (60.5 fold) while CEBPA does the same but to a lesser extent (RIG-I-26.4 fold, MDA5-10.8 fold, IFI16-l- 3.3 fold and cGAS-8.6 fold). CEBPB does not appear to have a role in the up-regulation of these genes. PU.1 expression also primes the cells to develop a strong immune response against the dsRNA virus mimic polyinosinic:polycytidylic acid (poly I:C) by significantly up-regulating Interferon-ß (14.9 fold change with p-value <0.0001). CEBPA up-regulates Interferon-ß to a lower level than PU.1 (4.7 fold change with p-value 0.0024), whereas CEBPB exhibits non-significant up-regulation (2.1 fold with p-value of 0.1449). As PU.1 robustly up-regulates the nucleic acid sensing pathways, it can prove to be useful in improving the defence against viruses that can cause losses to animal husbandry.
