Infected-host-cell repertoire and cellular response in the lung following inhalation of Francisella tularensis Schu S4, LVS, or U112.
Francisella tularensis causes systemic disease in humans and other mammals, with high morbidity and mortality associated with inhalation-acquired infection. F. tularensis is a facultative intracellular pathogen, but the scope and significance of cell types infected during disease is unknown. Using flow cytometry, we identified and quantified infected-cell types and assessed the impact of infection on cell populations following inhalation of F. tularensis strains U112, LVS, and Schu S4. Initially, alveolar macrophages comprised over 70% of Schu S4- and LVS-infected cells, whereas approximately 51% and 27% of U112-infected cells were alveolar macrophages and neutrophils, respectively. After 3 days, roughly half of Schu S4- and LVS- and nearly 80% of U112-infected cells were neutrophils. All strains infected CD11b(high) macrophages, dendritic cells, monocytes, and alveolar type II cells throughout infection. Macrophage, monocyte, and dendritic-cell populations were reduced during U112 infection but not Schu S4 or LVS infection. These results demonstrate directly that F. tularensis is a promiscuous intracellular pathogen in the lung that invades and replicates within cell types ranging from migratory immune cells to structural tissue cells. However, the proportions of cell types infected and the cellular immune response evoked by the human pathogenic strain Schu S4 differ from those of the human avirulent U112.
Hall
Joshua D
JD
Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7290, USA.
Woolard
Matthew D
MD
Gunn
Bronwyn M
BM
Craven
Robin R
RR
Taft-Benz
Sharon
S
Frelinger
Jeffrey A
JA
Kawula
Thomas H
TH
D000818:Animals; D003713:Dendritic Cells / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D005604:Francisella tularensis; D019570:Inhalation Exposure; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D016676:Macrophages, Alveolar / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000382:microbiology; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology*