Coxiella burnetii Subverts p62/Sequestosome 1 and Activates Nrf2 Signaling in Human Macrophages

Infection and Immunity
Caylin G WinchellDaniel E Voth

Abstract

Coxiella burnetii is the causative agent of human Q fever, a debilitating flu-like illness that can progress to chronic disease presenting as endocarditis. Following inhalation, C. burnetii is phagocytosed by alveolar macrophages and generates a lysosome-like replication compartment termed the parasitophorous vacuole (PV). A type IV secretion system (T4SS) is required for PV generation and is one of the pathogen's few known virulence factors. We previously showed that C. burnetii actively recruits autophagosomes to the PV using the T4SS but does not alter macroautophagy. In the current study, we confirmed that the cargo receptor p62/sequestosome 1 (SQSTM-1) localizes near the PV in primary human alveolar macrophages infected with virulent C. burnetii p62 and LC3 typically interact to select cargo for autophagy-mediated degradation, resulting in p62 degradation and LC3 recycling. However, in C. burnetii-infected macrophages, p62 was not degraded when cells were starved, suggesting that the pathogen stabilizes the protein. In addition, phosphorylated p62 levels increased, indicative of activation, during infection. Small interfering RNA experiments indicated that p62 is not absolutely required for intracellular growth, suggesting...Continue Reading

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Citations

Oct 10, 2018·Infection and Immunity·Jeremy BechelliRong Fang
Mar 19, 2021·Pathogens and Disease·Amanda L Dragan, Daniel E Voth
Nov 11, 2021·Pathogens and Disease·Robson Kriiger LoterioHayley J Newton

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