Identification of a tissue resident alveolar macrophage population susceptible to and permissive of Coxiella burnetii infection. (117.14)

Abstract

Abstract Intracellular bacteria, such as the US biological Class B bacterium Coxiella burnetii, are known to infect alveolar macrophages (AM). However, it is not known if a particular subset of AM, within a relatively heterogeneous population of lung macrophages, is particularly susceptible to bacterial infection. Nor is it known whether certain AM are less efficient at resolving infection. We hypothesized that, as a result of tightly regulated immune function, tissue resident AM would prove susceptible to C. burnetii infection and provide a required niche for bacterial persistence. Dye labeling techniques allowed discrimination of AM subsets during the course of infection. Infected cell populations were identified immunohistochemically and through the use of fluorescent protein expressing C. burnetii. We report here that the tissue resident AM are the predominantly infected AM subset, even at low infective doses; these cells remain infected at least nine days after the onset of infection, indicating a permissive niche for bacterial infection. These tissue resident AM undergo a distinguishing phenotypic change during the progression of infection and account for the cell-type predominating in the early uptake of Coxiella. Identification of the AM subset, both susceptible to and permissive of Coxiella burnetii infection, marks an important step in understanding Coxiella pathogenesis providing insight into general pulmonary innate immune function in response to intracellular bacteria.