PYHIN Protein Ifi207 Regulates RNA Polymerase II Activity at the Tnf Gene and Contributes to the Establishment of <i>Klebsiella pneumoniae</i> Infection

PYHIN proteins Aim2 and Ifi204 sense pathogen DNA, while other PYHINs have been shown to regulate host gene expression through as yet unclear mechanisms. We characterised mouse PYHIN Ifi207 which we found was upregulated in response to pattern recognition receptor (PRR) stimulation in myeloid cells. Ifi207 was not involved in DNA sensing but rather was required for PRR-stimulated Tnf induction. Ifi207 colocalised with active RNA polymerase II (Pol II) in the nucleus, and was required for Pol II transcriptional activity on the Tnf gene. Generation of Ifi207-/- mice showed no role for Ifi207 in autoimmunity, but did show that Ifi207 was required for Klebsiella pneumoniae-stimulated cytokine induction and for the bacteria to establish a lung infection. Thus PYHINS can have distinct roles in innate immunity independent of DNA sensing, as typified by Ifi207 which can directly engage with the transcriptional machinery to modulate cytokine responses.