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Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells
- Source :
- Infection and Immunity
- Publication Year :
- 2016
- Publisher :
- American Society for Microbiology, 2016.
-
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.
- Subjects :
- Cytotoxicity, Immunologic
0301 basic medicine
Burkholderia pseudomallei
Melioidosis
medicine.medical_treatment
Mice
Respiratory Tract Infections
Cells, Cultured
Virulence
biology
High-Throughput Nucleotide Sequencing
Respiratory infection
Bacterial Infections
060500 MICROBIOLOGY
3. Good health
Infectious Diseases
Cytokine
Neutrophil Infiltration
Host-Pathogen Interactions
Cytokines
Female
Tumor necrosis factor alpha
Signal Transduction
Virulence Factors
Immunology
Microbiology
Olfactory Receptor Neurons
03 medical and health sciences
Immunity
medicine
Animals
Humans
110707 Innate Immunity
Bacterial Capsules
Innate immune system
Gene Expression Profiling
Computational Biology
biology.organism_classification
medicine.disease
Bacterial Load
Immunity, Innate
Disease Models, Animal
030104 developmental biology
Mutation
Parasitology
Olfactory ensheathing glia
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 84
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....3420d6ac079c55222603886347e85945
- Full Text :
- https://doi.org/10.1128/iai.01546-15