Host Pathogen Interaction Between Human Neutrophils and Coxiella burnetii-An Intricate Webbed Affair

Date

2023

Authors

Thangamani, Kannan

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Abstract

Human Q-fever, caused by Coxiella burnetii and primarily transmitted through aerosol infection, typically results in flu-like symptoms and community-acquired pneumonia. Alveolar macrophages and neutrophils are primary responders to this infection. Previous research has extensively studied the ability of C. burnetii to subvert the immune defenses of human macrophages and mouse neutrophils. However, a knowledge gap exists in the role of human neutrophils in defense against this obligatory intracellular pathogen. Therefore, using human circulating neutrophils isolated from blood, we aimed to explore the ability of NMII strain C. burnetii to modulate its host survival and immune responses. In this study, we demonstrate that human neutrophils infected with 10 MOI and 100 MOI C. burnetii displayed a significant delay in the onset of apoptosis. Furthermore, human neutrophils infected with 100 MOI C. burnetii displayed induction of LC3 mediated autophagy. Inhibiting autophagy using wortmannin, a class III PI3k inhibitor, before the 100 MOI infection led to partial reinstatement of apoptosis, revealing the role of autophagy in mediating neutrophil fate. Additionally, live cell imaging revealed necrotic cell death in neutrophils in response to Coxiella burnetii infection. The extent of these NET like formation was significantly different between minimal 10 MOI infection and higher 100 MOI infection conditions. The 10 MOI infection caused local swarming and smaller NET deployments, paired with delayed apoptosis in non-NET releasing neutrophils, whereas 100 MOI infection caused an extensive lysis and NET like deployment trapping C. burnetii. This pro-inflammatory response of human neutrophils towards Coxiella burnetii is the first to have been�recorded. Further studying and manipulating neutrophil cell death can lead to better infection management as well as host recovery.

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Keywords

apoptosis, autophagy, Coxiella burnetii, human neutrophils, intracellular bacteria, neutrophil extracellular traps

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Department

Neuroscience, Developmental and Regenerative Biology