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Dando, Samantha J., Ipe, Deepak S., Batzloff, Michael, Sullivan, Matthew J. 
ORCID: https://orcid.org/0000-0003-2276-3132, Crossman, David K., Crowley, Michael, Strong, Emily, Kyan, Stephanie, Leclercq, Sophie Y., Ekberg, Jenny A. K., St. John, James, Beacham, Ifor R. and Ulett, Glen C.
(2016)
Burkholderia pseudomallei capsule exacerbates respiratory melioidosis but does not afford protection against antimicrobial signaling or bacterial killing in human olfactory ensheathing cells.
Infection and Immunity, 84 (7).
pp. 1941-1956.
ISSN 0019-9567
Abstract
Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an often severe infection that regularly involves respiratory disease following inhalation exposure. Intranasal (i.n.) inoculation of mice represents an experimental approach used to study the contributions of bacterial capsular polysaccharide I (CPS I) to virulence during acute disease. We used aerosol delivery of B. pseudomallei to establish respiratory infection in mice and studied CPS I in the context of innate immune responses. CPS I improved B. pseudomallei survival in vivo and triggered multiple cytokine responses, neutrophil infiltration, and acute inflammatory histopathology in the spleen, liver, nasal-associated lymphoid tissue, and olfactory mucosa (OM). To further explore the role of the OM response to B. pseudomallei infection, we infected human olfactory ensheathing cells (OECs) in vitro and measured bacterial invasion and the cytokine responses induced following infection. Human OECs killed >90% of the B. pseudomallei in a CPS I-independent manner and exhibited an antibacterial cytokine response comprising granulocyte colony-stimulating factor, tumor necrosis factor alpha, and several regulatory cytokines. In-depth genome-wide transcriptomic profiling of the OEC response by RNA-Seq revealed a network of signaling pathways activated in OECs following infection involving a novel group of 378 genes that encode biological pathways controlling cellular movement, inflammation, immunological disease, and molecular transport. This represents the first antimicrobial program to be described in human OECs and establishes the extensive transcriptional defense network accessible in these cells. Collectively, these findings show a role for CPS I in B. pseudomallei survival in vivo following inhalation infection and the antibacterial signaling network that exists in human OM and OECs.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work, including the efforts of Glen C. Ulett, was funded by Department of Industry, Innovation, Science, Research and Tertiary Education, Australian Government | Australian Research Council (ARC) (FT110101048). This work, including the efforts of Michael Batzloff, Ifor R. Beacham, and Glen C. Ulett, was funded by Department of Health | National Health and Medical Research Council (NHMRC) (APP1020394). SYL is supported by a Fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Brazil.GCUis supported by an Australian Research Council Future Fellowship. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: © 2016, American Society for Microbiology. |
| Uncontrolled Keywords: | parasitology,microbiology,immunology,infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2405 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Science > Research Groups > Molecular Microbiology Faculty of Medicine and Health Sciences > Research Groups > Pathogen Biology Group |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 15 Aug 2022 09:30 |
| Last Modified: | 25 Sep 2024 16:37 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/87233 |
| DOI: | 10.1128/IAI.01546-15 |
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