Journal article
Direct and Indirect Impairment of Human Dendritic Cell Function by Virulent Francisella tularensis Schu S4
Infection and immunity, Vol.77(1), pp.180-195
01/2009
Handle:
https://hdl.handle.net/2376/116398
PMCID: PMC2612294
PMID: 18981246
Abstract
The gram-negative, facultative intracellular bacterium
Francisella tularensis
causes acute, lethal pneumonic disease following infection with only 10 CFU. The mechanisms used by the bacterium to accomplish this in humans are unknown. Here, we demonstrate that virulent, type A
F. tularensis
strain Schu S4 efficiently infects and replicates in human myeloid dendritic cells (DCs). Despite exponential replication over time, Schu S4 failed to stimulate transforming growth factor β, interleukin-10 (IL-10), IL-6, IL-1β, IL-12, tumor necrosis factor alpha, alpha interferon (IFN-α), and IFN-β throughout the course of infection. Schu S4 also suppressed the ability of directly infected DCs to respond to different Toll-like receptor agonists. Furthermore, we also observed functional inhibition of uninfected bystander cells. This inhibition was mediated, in part, by a heat-stable bacterial component. Lipopolysaccharide (LPS) from Schu S4 was present in Schu S4-conditioned medium. However, Schu S4 LPS was weakly inflammatory and failed to induce suppression of DCs at concentrations below 10 μg/ml, and depletion of Schu S4 LPS did not significantly alleviate the inhibitory effect of Schu S4-conditioned medium in uninfected human DCs. Together, these data show that type A
F. tularensis
interferes with the ability of a central cell type of the immune system, DCs, to alert the host of infection both intra- and extracellularly. This suggests that immune dysregulation by
F. tularensis
operates on a broader and more comprehensive scale than previously appreciated.
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Details
- Title
- Direct and Indirect Impairment of Human Dendritic Cell Function by Virulent Francisella tularensis Schu S4
- Creators
- Jennifer C Chase - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840Jean Celli - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840Catharine M Bosio - Immunity to Pulmonary Pathogens Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840
- Publication Details
- Infection and immunity, Vol.77(1), pp.180-195
- Academic Unit
- Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900547434801842
- Language
- English
- Resource Type
- Journal article