Coxiella burnetii Requires Host Eukaryotic Initiation Factor 2{alpha} Activity for Efficient Intracellular Replication [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]

In this study, we investigated the impact of C. burnetii infection on activation of the three arms of the UPR. An inhibitor of the UPR antagonized PV expansion in macrophages, indicating this process is needed for bacterial replication niche formation. Protein kinase RNA-like ER kinase (PERK) signaling was activated during infection, leading to increased levels of phosphorylated eukaryotic initiation factor α, which was required for C. burnetii growth. Increased production and nuclear translocation of the transcription factor ATF4 also occurred, which normally drives expression of the proapoptotic C/EBP homologous protein (CHOP). CHOP protein production increased during infection; however, C. burnetii actively prevented CHOP nuclear translocation and downstream apoptosis in a T4SS-dependent manner. The results collectively demonstrate interplay between C. burnetii and specific components of the eIF2α signaling cascade to parasitize human macrophages.

Source: Infection and Immunity - June 21, 2020 Category: Infectious Diseases Authors: Brann, K. R., Fullerton, M. S., Voth, D. E. Tags: Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Source Type: research