Burkholderia pseudomallei Capsule Exacerbates Respiratory Melioidosis but Does Not Afford Protection against Antimicrobial Signaling or Bacterial Killing in Human Olfactory Ensheathing Cells.
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.
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Samantha J
SJ
Dando
Institute for Glycomics, Griffith University, Gold Coast, Australia.|School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Deepak S
DS
Ipe
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Michael
M
Batzloff
School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
Matthew J
MJ
Sullivan
Heflin Center for Human Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
David K
DK
Crossman
Heflin Center for Human Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Michael
M
Crowley
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Emily
E
Strong
Institute for Glycomics, Griffith University, Gold Coast, Australia.
Stephanie
S
Kyan
School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|Research and Development Center, Ezequiel Dias Foundation (FUNED), Belo Horizonte, MG, Brazil.
Sophie Y
SY
Leclercq
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.|Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
Jenny A K
JAK
Ekberg
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Australia.
James
J
St John
Institute for Glycomics, Griffith University, Gold Coast, Australia i.beacham@griffith.edu.au g.ulett@griffith.edu.au.
Ifor R
IR
Beacham
Institute for Glycomics, Griffith University, Gold Coast, Australia i.beacham@griffith.edu.au g.ulett@griffith.edu.au.|School of Medical Science, and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.|School of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Glen C
http://orcid.org/0000-0002-9638-8091
GC
Ulett
D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008554:Melioidosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009154:Mutation; D020556:Neutrophil Infiltration; D018034:Olfactory Receptor Neurons / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors
D016207:Cytokines; D037521:Virulence Factors