Nasal-associated lymphoid tissue and olfactory epithelium as portals of entry for Burkholderia pseudomallei in murine melioidosis.
BACKGROUND
Burkholderia pseudomallei, the causative agent of melioidosis, is generally considered to be acquired via inhalation of dust or water droplets from the environment. In this study, we show that infection of the nasal mucosa is potentially an important portal of entry in melioidosis.


METHODS
After intranasal inoculation of mice, infection was monitored by bioluminescence imaging and by immunohistological analysis of coronal sections. The bacterial loads in organ and tissue specimens were also monitored.


RESULTS
Bioluminescence imaging showed colonization and replication in the nasal cavity, including the nasal-associated lymphoid tissue (NALT). Analysis of coronal sections and immunofluorescence microscopy further demonstrated the presence of infection in the respiratory epithelium and the olfactory epithelium (including associated nerve bundles), as well as in the NALT. Of significance, the olfactory epithelium and the brain were rapidly infected before bacteria were detected in blood, and a capsule-deficient mutant infected the brain without significantly infecting blood.


CONCLUSIONS
These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.
Owen
Suzzanne J
SJ
Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
Batzloff
Michael
M
Chehrehasa
Fatemeh
F
Meedeniya
Adrian
A
Casart
Yveth
Y
Logue
Carie-Anne
CA
Hirst
Robert G
RG
Peak
Ian R
IR
Mackay-Sim
Alan
A
Beacham
Ifor R
IR
D000818:Animals; D016957:Burkholderia pseudomallei / Q000166:cytology; D002455:Cell Division; D005260:Female; D008164:Luminescent Proteins; D008221:Lymphoid Tissue / Q000382:microbiology*; D008554:Melioidosis / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009666:Nose / Q000033:anatomy & histology / Q000382:microbiology; D009830:Olfactory Bulb / Q000382:microbiology; D009831:Olfactory Mucosa / Q000382:microbiology*; D011984:Sensory Receptor Cells / Q000382:microbiology
D008164:Luminescent Proteins