Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells
| Autor: | Glen C. Ulett, Stephanie Kyan, Jenny Ekberg, Michael R. Batzloff, Michael J. Crowley, Emily Strong, Deepak S. Ipe, Ifor R. Beacham, Sophie Y. Leclercq, Matthew J. Sullivan, James Anthony St John, David K. Crossman, Samantha J. Dando |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
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 |
| Zdroj: | Infection and Immunity |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|