A Coxiella burnetii effector interacts with the host PAF1 complex and suppresses the innate immune response

Intracellular bacteria such as the pathogen Coxiella burnetii inject effector proteins into the host cell that promote productive infection. One common strategy of pathogen effectors is to suppress host immune responses to enable pathogen replication. The C. burnetii type IV secretion system translocates a large number of effectors into host cells that collectively promote intracellular bacterial replication, but the individual functions of most of these effectors are poorly understood. In this study, we describe a C. burnetii effector, CBU1314, that localizes to the nucleus and inhibits NF-{kappa}B-, MAPK-, and type I IFN-dependent gene expression. Mechanistically, we find that CBU1314 interacts with the PAF1 complex (PAF1C), a central host transcriptional complex that regulates expression of inflammatory genes in innate immune cells. Notably, we find that PAF1 promotes immune gene expression in response to various immune agonists and C. burnetii infection. Moreover, we find that PAF1 is critical for restricting intracellular C. burnetii replication. Overall, our findings uncover PAF1C as a host target of a C. burnetii effector and reveal new insight into how intracellular bacterial pathogens subvert cell- intrinsic innate defenses. SignificanceIntracellular bacteria often employ secreted effector proteins to modulate cellular processes and survive intracellularly. The study of these effectors can provide valuable insight into microbial pathogenesis and host biology. Here, we describe a Coxiella burnetii effector that inhibits multiple host signaling pathways and modulates the innate immune response. This effector interacts with the host PAF1 complex (PAF1C), a central regulator of transcription. Furthermore, we show that PAF1 is necessary for maximal gene expression downstream of various innate immune receptors and restricts bacterial replication during infection. Overall, our study elucidates the function of a C. burnetii effector in evading the immune response and provides insight into the role of PAF1C in cell-intrinsic defense against bacterial pathogens.