Coxiella burnetii Interaction with Neutrophils and Macrophages In Vitro and in SCID Mice following Aerosol Infection

Abstract

ABSTRACT Coxiella burnetii is an obligate intracellular bacterium that causes acute and chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol infection. However, there is a fundamental gap in the knowledge regarding the mechanisms of pulmonary immunity against C. burnetii infection. This study focused on understanding the interaction between C. burnetii and innate immune cells in vitro and in vivo . Both virulent C. burnetii Nine Mile phase I (NMI) and avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the infection rates were lower than 29%, suggesting that C. burnetii can infect neutrophils, but infection is limited. Interestingly, C. burnetii inside neutrophils can infect and replicate within macrophages, suggesting that neutrophils cannot kill C. burnetii and C. burnetii may be using infection of neutrophils as an evasive strategy to infect macrophages. To elucidate the mechanisms of the innate immune response to C. burnetii natural infection, SCID mice were exposed to aerosolized C. burnetii . Surprisingly, neutrophil influx into the lungs was delayed until day 7 postinfection in both NMI- and NMII-infected mice. This result suggests that neutrophils may play a unique role in the early immune response against aerosolized C. burnetii . Studying the interaction between C. burnetii and the innate immune system can provide a model system for understanding how the bacteria evade early immune responses to cause infection.